International Journal of
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Opinion Volume 4 Issue 1
P53 Mutational Signature in Cancer
Mukhtar Ullah
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University of the Punjab, Pakistan
Correspondence: Mukhtar Ullah, University of the Punjab, CAMB, 87 West Canal Bank Road Thokar Naiz Baig, Pakistan, Tel +923348834141
Received: January 12, 2017 | Published: January 16, 2017
Citation: Ullah M (2017) P53 Mutational Signature in Cancer. Int J Vaccines Vaccin 4(1): 00070. DOI: 10.15406/ijvv.2017.04.00070
Keywords
tumor, chromosome, tetramerization, oligomeric, acetyltransferases
Abbreviations
DNA, deoxyribonucleic acid; TD, tetramerization domain; DBD, DNA binding domain; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; HCC, hepatocellular carcinoma
Opinion
P53 is tumor suppressive gene located on chromosome no 17p13.1 and 20kb in size. This contains 11 exons and the first one is non-coding exon. The p53 protein contains five main domains: N-terminal Transactivation domain (1-61aa), Pro-rich domain (61-101aa), DNA binding domain (101-300aa), tetramerization domain (326-356aa) and C-terminal basic domain (364-393). The N-terminal transactivation domain TAD is required for activation of different transcription factor i.e. TFIID and TFIIH and also mediates the interaction with histone acetyltransferases CBP with E3 ubiquitin ligase MDM2. PRD play important role in p53 stability, transcription activation, and induction of transcription independent apoptosis, DBD is responsible for binding with the p53 co repressor. The TD involved in regulation of the oligomeric state of p53 and BD regulates the sequence specific binding of DBD. P53 act as polestar protein of complex signaling network that control cell proliferation, cell death in response to different stimuli, including DNA damage, nutrient deprivation, nucleotide depletion, hypoxia, oxidative stress, and hyper proliferative signals. Activated p53 perform their function in different ways. It acts as transcription factor to bind with the promoter region of different genes and regulate their expression level to induce cell cycle arrest, apoptosis, and DNA repair. The p53 is most commonly mutated protein that is almost found in all types of cancer. The mutation mainly occurs in DNA binding domain (DBD) followed by tetramerization domain (TD). The mutational signature of p53 in cancer is diverse. It is reported that all exon of p53 (1-11) can mutate but the most frequently mutated exons are 5, 7 and 8. The type of mutation in cancer is mainly missense, nonsense and deletion but the pattern of mutation is different in different ethnic group depends on the geographical location. Studies show that the 34 % of p53 mutation affect 10 residues 175, 176, 213, 220, 245, 248, 273 and 282 but the three are mainly 175, 248 and 273. More than 90% of all the p53 mutation in cancer occurs in central core region (codon 101-300). The following table show all reported p53 mutation in different cancer cell lines (Table 1).
Cell Line |
Cancer Type |
Mutation |
||
MDA-MB-468 |
Breast cancer |
CGGàTGG (273RàH) |
||
T-47D |
Breast cancer |
CTTàTTT (194LàF) |
||
MCF7 |
Breast cancer |
|||
Hs 578T |
Breast cancer |
GTCàTTC (157VàF) |
||
HCT 1 |
Colon cancer |
CàT (241SàF) |
||
DLD1 |
Colon cancer |
CGTàCAT (273RàH) |
||
SW620 |
Colon cancer |
CGTàCAT (273RàH) |
||
HT-29 |
Colon cancer |
CCCàTCC (309PàS) |
||
SW480 |
Colon cancer |
CGGàTGG (248RàW) |
||
COLO 320DM |
Colon cancer |
CGGàTGG (248RàW) |
||
866MT |
NSCLC |
TGTàTGA (229Càstop) |
||
A2182 |
NSCLC |
WT |
||
NCI-H292 |
NSCLC |
WT |
||
Calu6 |
NSCLC |
CGAàCGT (196Ràstop) |
||
A427 |
NSCLC |
WT |
||
Calu-1 |
NSCLC |
Deletion |
||
NCI-H358 |
NSCLC |
Deletion |
||
NCI-H1155 |
NSCLC |
CGTàCAT (273RàH) |
||
NCI-H157 |
NSCLC |
GàT (298Eàstop) |
>
||
NCI-H596 |
NSCLC |
GGCàTGC (245àC) |
||
A549 |
NSCLC |
WT |
||
NCI-N417 |
SCLS |
GAGàTAG (298Eàstop) |
||
MDS92 |
SCLS |
ATGàATA (237MàI) |
||
NCI-H446 |
SCLS |
WT |
||
NCI-H146 |
SCLS |
Splice junction of intron3 |
||
NCI-H82 |
SCLS |
GàC |
||
HA22T/VGH |
HCC |
Deletion |
||
HUH4 |
HCC |
121 Sàstop |
||
HEP 3B |
HCC |
Deletion |
||
HUH7 |
HCC |
TATàTGT (220Càstop) |
||
SK-HEP-1 |
HCC |
WT |
||
MIA PaCa-2 |
Pancreas cancer |
CGCàTGG (248RàH) |
||
Capan-2 |
Pancreas cancer |
CGTàCAT (273RàH) |
||
AsPC-1 |
Pancreas cancer |
CGTàCAT (273RàH) |
||
FaDu |
Oral cancer |
CGGàCTG (248RàL) |
||
SSC-4 |
Oral cancer |
CCC?CTC (151P?L) |
||
118 MG |
Glioblastoma |
GàA (213RàQ) |
||
HCE7 |
Esophagus cancer |
CàT (278PàS) |
||
Table 1 p53 mutation in different cancer cell lines
Acknowledgments
None.
Conflicts of interest
Author declares there are no conflicts of interest.
Funding
None.
©2017 Ullah. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.