International Journal of ISSN: 2470-9980IJVV

Vaccines & Vaccination
Opinion
Volume 4 Issue 1 - 2017
P53 Mutational Signature in Cancer
Mukhtar Ullah*
University of the Punjab, Pakistan
Received: January 12, 2017 | Published: January 16, 2017
*Corresponding author: Mukhtar Ullah, University of the Punjab, CAMB, 87 West Canal Bank Road Thokar Naiz Baig, Pakistan, Tel: +923348834141; Email:
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.

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