2 Structure: Tumor Protein p53, Also Known As p53, Cellular p53 (p53, Tumor Suppressor p53, Antigen NY-CO-13

P53
For other uses, see P53 (disambiguation).
suggested that TP53 codon 72 polymorphisms, MDM2

SNP309, and A2164G may collectively be associated
with non-oropharyngeal cancer susceptibility and that
MDM2 SNP309 in combination with TP53 codon 72
may accelerate the development of non-oropharyngeal
cancer in women.[13] A 2011 study found that TP53
codon 72 polymorphism was associated with an increased
risk of lung cancer.[14]
Tumor protein p53, also known as p53, cellular

tumor antigen p53 (UniProt name), phosphoprotein
p53, tumor suppressor p53, antigen NY-CO-13,
or transformation-related protein 53 (TRP53), is a
protein that is encoded by the TP53 gene in humans.
The p53 protein is crucial in multicellular organisms,
where it regulates the cell cycle and, thus, functions as
a tumor suppressor, preventing cancer. As such, p53 has
been described as the guardian of the genome" because
of its role in conserving stability by preventing genome
mutation.[2] Hence TP53 is classied as a tumor suppressor gene.[3][4][5][6]
Meta-analyses from 2011 found no signicant associations between TP53 codon 72 polymorphisms and both
colorectal cancer risk[15] and endometrial cancer risk.[16]
A 2011 study of a Brazilian birth cohort found an association between the non mutant arginine TP53 and individuals without a family history of cancer.[17] Another 2011
The name p53 is in reference to its apparent molecular study found that the p53 homozygous (Pro/Pro) genotype
a signicantly increased risk for renal
mass: SDS-PAGE analysis indicates that it is a 53- was associated with
[18]
cell
carcinoma.
kilodalton (kDa) protein. However, based on calculations
from its amino acid residues, p53s mass is actually only (Italics are used to denote the TP53 gene name and dis43.7 kDa. This dierence is due to the high number of tinguish it from the protein it encodes.)
proline residues in the protein; these slow its migration on
SDS-PAGE, thus making it appear heavier than it actually is.[7] This eect is observed with p53 from a variety 2 Structure
of species, including humans, rodents, frogs, and sh.
Gene
In humans, the TP53 gene is located on the short arm

of chromosome 17 (17p13.1).[3][4][5][6] The gene spans A schematic of the known protein domains in p53. (NLS = Nu20 kb, with a non-coding exon 1 and a very long rst in- clear Localization Signal).
tron of 10 kb. The coding sequence contains ve regions
showing a high degree of conservation in vertebrates, predominantly in exons 2, 5, 6, 7 and 8, but the sequences
found in invertebrates show only distant resemblance to
mammalian TP53.[8] TP53 orthologs[9] have been identied in most mammals for which complete genome data
are available.
In humans, a common polymorphism involves the substitution of an arginine for a proline at codon position
72. Many studies have investigated a genetic link between this variation and cancer susceptibility; however,
the results have been controversial. For instance, a metaanalysis from 2009 failed to show a link for cervical
cancer.[10] A 2011 study found that the TP53 proline
mutation did have a profound eect on pancreatic cancer risk among males.[11] A study of Arab women found
Crystal structure of four p53 DNA binding domains (as found in
that proline homozygosity at TP53 codon 72 is associ- the bioactive homo-tetramer) attand has seven domains:
ated with a decreased risk for breast cancer.[12] One study
1
FUNCTION
1. an acidic N-terminus transcription-activation domain (TAD), also known as activation domain

1 (AD1), which activates transcription factors:
residues 1-42. The N-terminus contains two complementary transcriptional activation domains, with
a major one at residues 142 and a minor one at
residues 5575, specically involved in the regulation of several pro-apoptotic genes.[19]
2. activation domain 2 (AD2) important for apoptotic
activity: residues 43-63.
3. Proline rich domain important for the apoptotic ac- Mutations that deactivate p53 in cancer usually occur in
the DBD. Most of these mutations destroy the ability
tivity of p53: residues 64-92.
of the protein to bind to its target DNA sequences, and
thus prevents transcriptional activation of these genes. As
4. central DNA-binding core domain (DBD). Contains such, mutations in the DBD are recessive loss-of-function
one zinc atom and several arginine amino acids: mutations. Molecules of p53 with mutations in the OD
residues 102-292. This region is responsible for dimerise with wild-type p53, and prevent them from activating transcription. Therefore OD mutations have a
binding the p53 co-repressor LMO3.[20]
dominant negative eect on the function of p53.
5. nuclear localization signaling domain, residues 316325.
Wild-type p53 is a labile protein, comprising folded

and unstructured regions that function in a synergistic
manner.[26]
6. homo-oligomerisation domain (OD): residues 307355. Tetramerization is essential for the activity of
p53 in vivo.
3 Function
7. C-terminal involved in downregulation of DNA

binding of the central domain: residues 356-393.[21]
p53 has many mechanisms of anticancer function, and

plays a role in apoptosis, genomic stability, and inhibition of angiogenesis. In its anti-cancer role, p53 works
through several mechanisms:
A tandem of nine-amino-acid transactivation domains

(9aaTAD) was identied in the AD1 and AD2 regions of
transcription factor p53.[22] KO mutations and position
for p53 interaction with TFIID are listed below:[23]
It can activate DNA repair proteins when DNA has

sustained damage. Thus, it may be an important factor in aging.[27]
It can arrest growth by holding the cell cycle at the
G1/S regulation point on DNA damage recognition
(if it holds the cell here for long enough, the DNA
repair proteins will have time to x the damage and
the cell will be allowed to continue the cell cycle).
It can initiate apoptosis - programmed cell death - if
DNA damage proves to be irreparable.
Activated p53 binds DNA and activates expression

of several genes including microRNA miR-34a,[28]
WAF1/CIP1 encoding for p21 and hundreds of other
down-stream genes. p21 (WAF1) binds to the G1S/CDK (CDK4/CDK6, CDK2, and CDK1) complexes
(molecules important for the G1/S transition in the cell
9aaTADs mediate p53 interaction with general coactiva- cycle) inhibiting their activity.
tors - TAF9, CBP/p300 (all four domains KIX, TAZ1, When p21(WAF1) is complexed with CDK2 the cell canTAZ2 and IBiD), GCN5 and PC4, regulatory protein not continue to the next stage of cell division. A mutant
MDM2 and replication protein A (RPA).[24][25]
p53 will no longer bind DNA in an eective way, and,
3
a conformational change forces p53 to be activated as a
transcription regulator in these cells. The critical event
leading to the activation of p53 is the phosphorylation of
its N-terminal domain. The N-terminal transcriptional
activation domain contains a large number of phosphorylation sites and can be considered as the primary target
for protein kinases transducing stress signals.
The protein kinases that are known to target this transcriptional activation domain of p53 can be roughly divided into two groups. A rst group of protein kinases
belongs to the MAPK family (JNK1-3, ERK1-2, p38
MAPK), which is known to respond to several types of
stress, such as membrane damage, oxidative stress, osmotic shock, heat shock, etc. A second group of protein kinases (ATR, ATM, CHK1 and CHK2, DNA-PK,
CAK, TP53RK) is implicated in the genome integrity
checkpoint, a molecular cascade that detects and rep53 pathway: In a normal cell p53 is inactivated by its negative
sponds to several forms of DNA damage caused by genoregulator, mdm2. Upon DNA damage or other stresses, various
pathways will lead to the dissociation of the p53 and mdm2 com- toxic stress. Oncogenes also stimulate p53 activation,
plex. Once activated, p53 will induce a cell cycle arrest to allow mediated by the protein p14ARF.
either repair and survival of the cell or apoptosis to discard the In unstressed cells, p53 levels are kept low through a condamaged cell. How p53 makes this choice is currently unknown. tinuous degradation of p53. A protein called Mdm2 (also
called HDM2 in humans), which is itself a product of
p53, binds to p53, preventing its action and transports
as a consequence, the p21 protein will not be available to
it from the nucleus to the cytosol. Also Mdm2 acts as
act as the stop signal for cell division.[29] Studies of huubiquitin ligase and covalently attaches ubiquitin to p53
man embryonic stem cells (hESCs) commonly describe
and thus marks p53 for degradation by the proteasome.
the nonfunctional p53-p21 axis of the G1/S checkpoint
However, ubiquitylation of p53 is reversible.
pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, A ubiquitin specic protease, USP7 (or HAUSP), can
p21 mRNA is clearly present and upregulated after the cleave ubiquitin o p53, thereby protecting it from
DDR in hESCs, but p21 protein is not detectable. In this proteasome-dependent degradation. This is one means
cell type, p53 activates numerous microRNAs (like miR- by which p53 is stabilized in response to oncogenic in302a, miR-302b, miR-302c, and miR-302d) that directly sults. USP42 has also been shown to deubiquitinate p53
and may be required for the ability of p53 to respond to
inhibit the p21 expression in hESCs.[30]
stress.[36]
Recent research has also linked the p53 and RB1 pathways, via p14ARF, raising the possibility that the path- Recent research has shown that HAUSP is mainly localized in the nucleus, though a fraction of it can be found
ways may regulate each other.[31]
in the cytoplasm and mitochondria. Overexpression of
p53 by regulating LIF has been shown to faciliHAUSP results in p53 stabilization. However, depletion
tate implantation in the mouse model and possibly in
of HAUSP does not result to a decrease in p53 levels but
[32]
humans.
rather increases p53 levels due to the fact that HAUSP
p53 expression can be stimulated by UV light, which also binds and deubiquitinates Mdm2. It has been shown that
causes DNA damage. In this case, p53 can initiate events HAUSP is a better binding partner to Mdm2 than p53 in
leading to tanning.[33][34]
unstressed cells.
USP10 however has been shown to be located in the
cytoplasm in unstressed cells and deubiquitinates cyptoplasmic p53, reversing Mdm2 ubiquitination. Follow4 Regulation
ing DNA damage, USP10 translocates to the nucleus and
contributes to p53 stability. Also USP10 does not interact
p53 becomes activated in response to myriad stressors,
with Mdm2.[37]
including but not limited to DNA damage (induced by
either UV, IR, or chemical agents such as hydrogen per- Phosphorylation of the N-terminal end of p53 by
oxide), oxidative stress,[35] osmotic shock, ribonucleotide the above-mentioned protein kinases disrupts Mdm2depletion, and deregulated oncogene expression. This ac- binding. Other proteins, such as Pin1, are then recruited
tivation is marked by two major events. First, the half- to p53 and induce a conformational change in p53, which
life of the p53 protein is increased drastically, leading to prevents Mdm2-binding even more. Phosphorylation
a quick accumulation of p53 in stressed cells. Second, also allows for binding of transcriptional coactivators,
6 EXPERIMENTAL ANALYSIS OF P53 MUTATIONS
like p300 and PCAF, which then acetylate the carboxyterminal end of p53, exposing the DNA binding domain of p53, allowing it to activate or repress specic
genes. Deacetylase enzymes, such as Sirt1 and Sirt7, can
deacetylate p53, leading to an inhibition of apoptosis.[38]
Some oncogenes can also stimulate the transcription of
proteins that bind to MDM2 and inhibit its activity.
Role in disease
Survival Factors
(e.g., IGF1)
Chemokines,
Hormones,
Transmitters
(e.g., interleukins,
serotonin, etc.)
Growth Factors
(e.g., TGF, EGF)
Extracellular
Matrix
GPCR
RTK
G-Protein
Cytokine Receptor
PKA
IB
JAKs
Raf
Adenylate
cyclase
Dishevelled
FAK
Src
Ras
GSK-3
MEK
MEKK
MAPK
MKK
-catenin
STAT3,5
TCF
Myc: Mad:
Max Max
Bcl-xL
ERK JNKs
CREB
Gli
CycID
p16
Rb CDK4
p15
Caspase 9
Gene Regulation
Apoptosis
Caspase 8
FADD
p53
Bad
FasR
ARF
mdm2
Bcl-2
Abnormality
Sensor
Mt
-catenin:TCF
Jun
Cell
Proliferation
SMO
Fos
Cytochrome C
Hedgehog
APC
Patched
Cytokines
(e.g., EPC)
PKC
NF-B
Wnt
Fyn/Shc
Frizzled
Akt
cdc42
Grb2/SOS
PI3K
Akk
Integrins
RTK
PLC
E2F
CyclE
CDK2
p27
p21
Bax
Bim
Death factors
(e.g. FasL, Tnf)
Overview of signal transduction pathways involved in apoptosis.
A micrograph showing cells with abnormal p53 expression

(brown) in a brain tumor. p53 immunostain.
it can cause premature aging.[41] Restoring endogenous

normal p53 function holds some promise. Research
has showed that this restoration can lead to regression
of certain cancer cells without damaging other cells in
the process. The ways by which tumor regression occurs depends mainly on the tumor type. For example,
restoration of endogenous p53 function in lymphomas
may induce apoptosis, while cell growth may be reduced to normal levels. Thus, pharmacological reactivation of p53 presents itself as a viable cancer treatment option.[42][42][43] The rst commercial gene therapy,
Gendicine, was approved in China in 2003 for the treatment of head and neck squamous cell carcinoma. It delivers a functional copy of the p53 gene using an engineered
adenovirus.[44]
Certain pathogens can also aect the p53 protein that the
TP53 gene expresses. One such example, human papillomavirus (HPV), encodes a protein, E6, which binds to
the p53 protein and inactivates it. This mechanism, in
synergy with the inactivation of the cell cycle regulator
pRb by the HPV protein E7, allows for repeated cell division manifested clinically as warts. Certain HPV types,
in particular types 16 and 18, can also lead to progression from a benign wart to low or high-grade cervical
dysplasia, which are reversible forms of precancerous lesions. Persistent infection of the cervix over the years can
cause irreversible changes leading to carcinoma in situ
and eventually invasive cervical cancer. This results from
the eects of HPV genes, particularly those encoding E6
and E7, which are the two viral oncoproteins that are preferentially retained and expressed in cervical cancers by
integration of the viral DNA into the host genome.[45]
The p53 protein is continually produced and degraded in
cells of healthy people. The degradation of the p53 protein is associated with binding of MDM2. In a negative
feedback loop, MDM2 itself is induced by the p53 protein. Mutant p53 proteins often fail to induce MDM2,
causing p53 to accumulate at very high levels. Moreover, the mutant p53 protein itself can inhibit normal
p53 protein levels. In some cases, single missense mutations in p53 have been shown to disrupt p53 stability
and function.[46]
If the TP53 gene is damaged, tumor suppression is

severely compromised. People who inherit only one
functional copy of the TP53 gene will most likely develop tumors in early adulthood, a disorder known as LiFraumeni syndrome.
The TP53 gene can also be modied by mutagens
(chemicals, radiation, or viruses), increasing the likeli- 6 Experimental analysis of p53
hood for uncontrolled cell division. More than 50 permutations
cent of human tumors contain a mutation or deletion of
the TP53 gene.[39] Loss of p53 creates genomic instability
that most often results in an aneuploidy phenotype.[40]
Most p53 mutations are detected by DNA sequencing.
Increasing the amount of p53 may seem a solution for However, it is known that single missense mutations can
treatment of tumors or prevention of their spreading. have a large spectrum from rather mild to very severe
This, however, is not a usable method of treatment, since functional eects.[46]
Discovery
p53 was identied in 1979 by Lionel Crawford, David

P. Lane, Arnold Levine, and Lloyd Old, working at
Imperial Cancer Research Fund (UK) Princeton University/UMDNJ (Cancer Institute of New Jersey), and
Memorial Sloan-Kettering Cancer Center, respectively.
It had been hypothesized to exist before as the target of
the SV40 virus, a strain that induced development of tumors. The TP53 gene from the mouse was rst cloned
by Peter Chumakov of the Russian Academy of Sciences
in 1982,[47] and independently in 1983 by Moshe Oren
in collaboration with David Givol (Weizmann Institute
of Science).[48][49] The human TP53 gene was cloned in
1984[3] and the full length clone in 1985.[50]
It was initially presumed to be an oncogene due to the
use of mutated cDNA following purication of tumour
cell mRNA. Its character as a tumor suppressor gene was
nally revealed in 1989 by Bert Vogelstein working at
Johns Hopkins School of Medicine.[51]
Warren Maltzman, of the Waksman Institute of Rutgers
University rst demonstrated that TP53 was responsive to
DNA damage in the form of ultraviolet radiation.[52] In a
series of publications in 1991-92, Michael Kastan, Johns
Hopkins University, reported that TP53 was a critical part
of a signal transduction pathway that helped cells respond
to DNA damage.[53]
In 1993, p53 was voted molecule of the year by Science
magazine.[54]
The p21 protein binds directly to cyclin-CDK complexes
that drive forward the cell cycle and inhibits their kinase
activity thereby causing cell cycle arrest to allow repair to
take place. p21 can also mediate growth arrest associated
with dierentiation and a more permanent growth arrest
associated with cellular senescence. The p21 gene contains several p53 response elements that mediate direct
binding of the p53 protein, resulting in transcriptional activation of the gene encoding the p21 protein.
Interactions
p53 has been shown to interact with:

AIMP2,[55]
ANKRD2,
[56]
APTX,
[57]
BAK1,[66]
BARD1,[67]
BLM,[68][69][70][71]
BRCA1,[67][72][73][74][75]
BRCA2,[67][76]
BRCC3,[67]
BRE,[67]
CEBPZ,[77]
CDC14A,[78]
Cdk1,[79][80]
CFLAR,[81]
CHEK1,[68][82][83]
CCNG1,[84]
CREBBP,[85][86][87]
CREB1,[87]
Cyclin H,[88]
CDK7,[88][89]
DNA-PKcs,[59][82][90]
E4F1,[91][92]
EFEMP2,[93]
EIF2AK2,[94]
ELL,[95]
EP300,[86][96][97][98]
ERCC6,[99][100]
GNL3,[101]
GPS2,[102]
GSK3B,[103]
HSP90AA1,[104][105][106]
HIF1A,[107][108][109][110]
HIPK1,[111]
HIPK2,[112][113]
HMGB1,[114][115]
ATM,[58][59][60][61][62]
HSPA9,[116]
ATR,[58][59]
Huntingtin,[117]
ATF3,[63][64]
ING1,[118][119]
AURKA,[65]
ING4,[120][121]
INTERACTIVE PATHWAY MAP
ING5,[120]
SMARCA4,[161]
IB,[122]
SMARCB1,[161]
KPNB1,[104]
SMN1,[162]
LMO3,[20]
STAT3,[135]
Mdm2,[85][123][124][125]
TBP,[163][164]
MDM4,[126][127]
TFAP2A,[165]
MED1,[128][129]
TFDP1,[166]
MAPK9,[130][131]
TIGAR,[167]
MNAT1,[89]
TOP1,[168][169]
NDN,[132]
TOP2A,[170]
NCL,[133]
TP53BP1,[68][171][172][173][174][175][176]
NUMB,[134]
TP53BP2,[176][177]
NF-B,[135]
TOP2B,[170]
P16,[91][125][136]
TP53INP1,[178][179]
PARC,[137]
TSG101,[180]
PARP1,[57][138]
UBE2A,[181]
PIAS1,[93][139]
UBE2I,[93][159][182][183]
CDC14B,[78]
UBC,[55][149][160][184][185][186][187][188]
PIN1,[140][141]
USP7,[189]
PLAGL1,[142]
WRN,[71][190]
PLK3,[143][144]
WWOX,[191]
PRKRA,[145]
XPB,[99]
PHB,[146]
YBX1,[56][192]
PML,[123][147][148]
YPEL3,[193]
PSME3,[149]
YWHAZ,[194]
PTEN,[124]
Zif268,[195]
PTK2,[150]
ZNF148,[196]
PTTG1,[151]
RAD51,[67][152][153]
RCHY1,[154][155]
RELA,[135]
Reprimo
RPA1,[156][157]
RPL11,[136]
S100B,[158]
SUMO1,[159][160]
9 Interactive pathway map

Click on genes, proteins and metabolites below to link to
respective articles. [ 1]
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10
REFERENCES
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[1] The interactive pathway map can be edited at WikiPathways: FluoropyrimidineActivity_WP1601.
10 References
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Biology (IMCB), Singapore. p53 Knowledgebase
[Retrieved 2008-04-06].
GeneReviews/NCBI/NIH/UW
Fraumeni Syndrome
entry
on
Li-
TUMOR PROTEIN p53 @ OMIM

p53 restoration of function
p53 @ The Atlas of Genetics and Cytogenetics in
Oncology and Haematology
TP53 Gene @ GeneCards
p53 News provided by insciences organisation
David S. Goodsell. RCSB Protein Data Bank. p53
Tumor Suppressor; 2002-07-01 [Retrieved 200804-06].
Thierry Soussi. p53 Web Site [Retrieved 2008-0406].
The George Pantziarka TP53 Trust A support group
from the UK for suerers of Li-Fraumeni Syndrome
or other TP53-related disorders
18
IARC TP53 Somatic Mutations database maintained at IARC, Lyon, by Magali Olivier
11
EXTERNAL LINKS
19
12
12.1
Text and image sources, contributors, and licenses

Text
P53 Source: http://en.wikipedia.org/wiki/P53?oldid=644664105 Contributors: AxelBoldt, Magnus Manske, Sodium, 168..., Snoyes, Angela, JWSchmidt, Habj, MichaK, Quizkajer, Anupamsr, Pir, Peak, Fuelbottle, Diberri, Timemutt, Giftlite, Curps, Jfdwol, AlistairMcMillan, Onco p53, DragonySixtyseven, Vogon77, Jcorgan, Rich Farmbrough, Inkypaws, Wk muriithi, Cyclopia, Pabloes, Bobo192,
Grue, Truthux, Arcadian, Hargrimm, Oasisbob, Eric Kvaalen, Wouterstomp, Seans Potato Business, Aranae, ClockworkSoul, Danhash,
RyanGerbil10, Stemonitis, Woohookitty, Georgia guy, Carcharoth, Ekem, EnSamulili, Jarwulf, BorisTM, Rjwilmsi, Biochemza, Bruce1ee,
PhatRita, FlaBot, Kertrats, Siddhant, YurikBot, Spaully, Splette, Hydrargyrum, Draeco, Gwaihir, Snek01, Dtrebbien, NickBush24,
Nephron, Daniel Mietchen, Zwobot, Saric, JOK, HereToHelp, Banus, Xanin, GrinBot, Snalwibma, SmackBot, Kjaergaard, Timotheus Canens, Zephyris, Betacommand, Eug, Teemu08, The Rogue Penguin, Donaldal, JonHarder, T-borg, Drphilharmonic, Jls043, Rockpocket,
Clicketyclack, Madeleine Price Ball, Nishkid64, DO11.10, John, FrozenMan, SvenskaJohannes, Jaganath, XP528, Kyoko, Serephine,
Elb2000, Kvng, Abramsonj, Martious, Baloglu, Doppler89, Kevin Murray, Fvasconcellos, Measure4Measure, Maxxicum, Vectro, Anthonyhcole, Bgamari, Renji143, Daviddecraene, Izyt, Openlander, David D., AntiVandalBot, Vic226, Michael Ly, Ph.eyes, Cyningaenglisc,
TransControl, Magioladitis, Memeri, Sarahj2107, Joerogel, WhatamIdoing, Emw, Ohwell32, Fivins, Stolsvik, C4dn, AstarothCY, R'n'B,
Nono64, AlphaEta, Nbauman, Boghog, Maurice Carbonaro, Leif Halvorsen, Dr d12, Mikael Hggstrm, Mattximus, Xarqi, Imaginary Pi
Slicer, Iriskye, TallFreak, Enix150, Adm820, VolkovBot, Andrew Su, A4bot, Agricola44, Mclover08, Sintaku, SelketBot, Depelbaum007,
Egelner, BotKung, Carlifenkm, Alexbateman, Hedgehog33, Thierry Soussi, Cmcnicoll, Temporaluser, Twooars, AlleborgoBot, ProteinBoxBot, Marashie, Ivan tambuk, VVVBot, Bform, JonSDSUGrad, Lightmouse, Forluvoft, Ani81, Lutetium, KristinaHanspers, Meehanj5, H Sapien, Johnuniq, DumZiBoT, YouRang?, Jorgeq13, Addbot, DOI bot, Quercus solaris, Legobot, Luckas-bot, Yobot, Citation
bot, Shcha, GrouchoBot, Piskacek, Danfa1971, FrescoBot, Jatlas, D'ohBot, Citation bot 1, Xbcj0843hck3, 10metreh, PaoloRomano, RedBot, MastiBot, Yeast2Hybrid, Genypholy, LesterFreamon00, 777sms, Jesse V., RjwilmsiBot, Dancojocari, Kariohlsen, Rmelder, ZroBot,
AManWithNoPlan, WeigelaPen, RE73, ChuispastonBot, FeatherPluma, Ying Quliang, ClueBot NG, Oramg, Temmyr, Maadikhah, Helpful
Pixie Bot, ScienceFusion, M0rphzone, Vokesk, Mschelman, Davidthelion2, Thegreatgrabber, BattyBot, Jessthecat2610, ChrisGualtieri,
Vlsnewman, Aerist, Gordonfon, Everything Is Numbers, ComfyKem, David P Minde, Randykitty, Kardinc, Sunny0208, Hherce, Snsturgeon, Sbchristianlowe, Monkbot, Emileemagnusen, RaihaT, Rhodrijones93, Trent28, Kiraar ar, Mlhtml and Anonymous: 169
12.2
Images
File:3KMD_p53_DNABindingDomian.png
Source:
http://upload.wikimedia.org/wikipedia/commons/4/4a/3KMD_p53_
DNABindingDomian.png License: CC BY-SA 3.0 Contributors: Own work Original artist: Richard Wheeler (Zephyris)
File:Anaplastic_astrocytoma_-_p53_-_very_high_mag.jpg
Source:
http://upload.wikimedia.org/wikipedia/commons/8/82/
Anaplastic_astrocytoma_-_p53_-_very_high_mag.jpg License: CC BY-SA 3.0 Contributors: Own work Original artist: Nephron
File:Commons-logo.svg Source: http://upload.wikimedia.org/wikipedia/en/4/4a/Commons-logo.svg License: ? Contributors: ? Original
artist: ?
File:P53.png Source: http://upload.wikimedia.org/wikipedia/commons/b/bb/P53.png License: CC BY-SA 3.0 Contributors: Based on
atomic coordinates of PDB 1TUP, rendered with open source molecular visualization tool PyMol (www.pymol.org) Original artist: Thomas
Splettstoesser
File:P53_Schematic.tif Source: http://upload.wikimedia.org/wikipedia/commons/7/7e/P53_Schematic.tif License: CC BY-SA 3.0 Contributors: Own work Original artist: RaihaT
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File:PDB_1a1u_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/2/2c/PDB_1a1u_EBI.jpg License: Public domain
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1a1u/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
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1aie/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
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1olg/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
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1olh/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
20
12
TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES
File:PDB_1pes_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/e/e2/PDB_1pes_EBI.jpg License: Public domain

Contributors: http://www.ebi.ac.uk/pdbe-srv/view/images/entry/1pes600.png, displayed on http://www.ebi.ac.uk/pdbe-srv/view/entry/
1pes/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1pet_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/c/c7/PDB_1pet_EBI.jpg License: Public domain
Contributors: http://www.ebi.ac.uk/pdbe-srv/view/images/entry/1pet600.png, displayed on http://www.ebi.ac.uk/pdbe-srv/view/entry/
1pet/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1sae_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/8/88/PDB_1sae_EBI.jpg License: Public domain
Contributors: http://www.ebi.ac.uk/pdbe-srv/view/images/entry/1sae600.png, displayed on http://www.ebi.ac.uk/pdbe-srv/view/entry/
1sae/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1saf_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/4/45/PDB_1saf_EBI.jpg License: Public domain
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1saf/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1sag_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/f/fe/PDB_1sag_EBI.jpg License: Public domain
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1sag/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1sah_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/a/ae/PDB_1sah_EBI.jpg License: Public domain
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1sah/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1sai_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/9/93/PDB_1sai_EBI.jpg License: Public domain Contributors: http://www.ebi.ac.uk/pdbe-srv/view/images/entry/1sai600.png, displayed on http://www.ebi.ac.uk/pdbe-srv/view/entry/1sai/
summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1saj_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/9/9f/PDB_1saj_EBI.jpg License: Public domain
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1saj/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
File:PDB_1sak_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/f/f5/PDB_1sak_EBI.jpg License: Public domain
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1sak/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
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File:PDB_1tsr_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/5/54/PDB_1tsr_EBI.jpg License: Public domain Contributors: http://www.ebi.ac.uk/pdbe-srv/view/images/entry/1tsr600.png, displayed on http://www.ebi.ac.uk/pdbe-srv/view/entry/1tsr/
File:PDB_1tup_EBI.jpg Source: http://upload.wikimedia.org/wikipedia/commons/1/1b/PDB_1tup_EBI.jpg License: Public domain
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1tup/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
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2ahi/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
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2bio/summary Original artist: Jawahar Swaminathan and MSD sta at the European Bioinformatics Institute
12.3
Content license
21
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Contributors: http://www.ebi.ac.uk/pdbe-srv/view/images/entry/2bip600.png, displayed on http://www.ebi.ac.uk/pdbe-srv/view/entry/
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2 Structure: Tumor Protein p53, Also Known As p53, Cellular p53 (p53, Tumor Suppressor p53, Antigen NY-CO-13

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2 Structure: Tumor Protein p53, Also Known As p53, Cellular p53 (p53, Tumor Suppressor p53, Antigen NY-CO-13

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P53

For other uses, see P53 (disambiguation).

suggested that TP53 codon 72 polymorphisms, MDM2

Tumor protein p53, also known as p53, cellular

In humans, the TP53 gene is located on the short arm

1. an acidic N-terminus transcription-activation domain (TAD), also known as activation domain

Wild-type p53 is a labile protein, comprising folded

7. C-terminal involved in downregulation of DNA

p53 has many mechanisms of anticancer function, and

A tandem of nine-amino-acid transactivation domains

It can activate DNA repair proteins when DNA has

Activated p53 binds DNA and activates expression

6 EXPERIMENTAL ANALYSIS OF P53 MUTATIONS

Overview of signal transduction pathways involved in apoptosis.

A micrograph showing cells with abnormal p53 expression

it can cause premature aging.[41] Restoring endogenous

If the TP53 gene is damaged, tumor suppression is

p53 was identied in 1979 by Lionel Crawford, David

p53 has been shown to interact with:

INTERACTIVE PATHWAY MAP

9 Interactive pathway map

[10] Klug SJ, Ressing M, Koenig J, Abba MC, Agoras\ VM,

[32] Hu W, Feng Z, Teresky AK, Levine AJ (2007). p53

[33] Genomes guardian gets a tan started. March 17, 2007

[46] Bullock AN, Henckel J, DeDecker BS, Johnson

[34] Cui R, Widlund HR, Feige E, Lin JY, Wilensky DL,

[58] Fabbro M, Savage K, Hobson K, Deans AJ, Powell

[59] Kim ST, Lim D S, Canman C E, Kastan M B (1999).

[69] Wang XW, Tseng A, Ellis N A, Spillare E A, Linke S P,

[60] Kang J, Ferguson David, Song Hoseok, Bassing Craig,

[70] Garkavtsev IV, Kley N, Grigorian I A, Gudkov A V

[61] Khanna KK, Keating K E, Kozlov S, Scott S, Gatei M,

[71] Yang Q, Zhang Ran, Wang Xin Wei, Spillare Elisa A,

[62] Westphal CH, Schmaltz C, Rowan S, Elson A, Fisher D

[63] Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck

[74] Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao V N

[84] Zhao L, Samuels Tina, Winckler Sarah, Korgaonkar

lization of wild-type p53 by hypoxia-inducible factor

screening with p73 identies novel SUMO-1-interacting

[176] Iwabuchi K, Bartel P L, Li B, Marraccino R, Fields S

[186] Yang W, Dicker David T, Chen Jiandong, El-Deiry Wak

Lane Group at the Institute of Molecular and Cell

TUMOR PROTEIN p53 @ OMIM

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