Majority of cancer lead by point mutation in p53 gene. which is also known as "guardian of genome". this mutation leads conversion of normal cell into cancerous cell.

1. Activity of p53 in Cancer
Progression and metastasis
By
Ashish Kumar
M.Tech 1st year

2. OUTLINE
• CANCER Introduction
• Structure of p53
• Function of p53
• Literature Review
• Conclusion
• References
• Summary
• Questionnaire

3. Objective
• To give knowledge of cancer along with brief
description of p53 gene

4. Current Scenario
• In 2012, an estimated 14.1 million new cases of cancer
occurred worldwide.
• Out of 10 deaths 4 from cancer
• There are 100 different forms of cancer.
• Most common types of cancer are lung, breast, bowel and
prostate which accounts for 4 death in 10 cancer patients
• Lung cancer is common in Men’s and Breast cancer in Female

5. Cancer
• Single type of cell proliferate continuously
becomes immortal further into a tumor.
• Two types of tumor
– Benign Tumor
– Malignant Tumor

6. Who controls cancer in our body?

7. p53 Gene
• "the guardian of the genome"
• TP53 gene is located on the short arm
of chromosome 17 (17p13.1)
• TP53 gene encodes at least 15 protein
isoforms [1]
• Actual molecular weight is 43.7 kda [2]

8. P53 protein Structure
N-Terminus C-Terminus

9. p53 helps in cell repair mechanism
p53 Gene
p53 Gene
Continues cell division
P53 Gene Stop’s
the cell Division
Halt’s the cell
Cell Cycle
Heavy Damage
Minor Damage

10. p53 Gene p53 Protein p53 protein binds to DNA
p21 Gene
p21 Protein
Stimulates p21 gene
p21 Protein blocks CDK-2
MOLECULAR APPROACH [3]

11. Inhibition during Cell Division
CDK-2
p21 inhibits CDK-2
p53 P21 protein
Damage cell
APOPTOSIS

12. RISE OF MUTATED p53 THROUGH
BASE MUTATION/ POINT MUTATION

13. INACTIVATION OF NORMAL p53 AND
ACTIVATION OF MUTATED p53
N-Terminus
C-Terminus
Point Mutation Acquires GOF

14. RECRUITMENT MECHANISM TO THE PROMOTER
• To analyze GOF
• mtp53 can be recruited to promoters via interaction with
other transcriptional factors acc. to [4,5,6,7,8]
• Binding factors- E2F1, NF-Y, VDR, ETS1, ETS2, and
SP1 also binds with normal p53 acc. To [4,5,6,7,8,9]
• Mtp53 gene expression with help MRD1 promoter and
stated ETS-1 can interact with mtp53 not with normal
p53. ETS factor is require for transcriptional regulatory
activity of mtp53. [10]
• Other studies revealed ETS1 also require to
normal p53 gene for transcription regularities.

15. DOMAIN REQUIREMENTS FOR MUTANT p53
TRANSCRIPTIONALLY DEPENDENT GOF [8,15]

17. CONCLUSION
• ETS and mtp53 help each other for their profit.

18. Reference
• 1 Surget S, Khoury MP, Bourdon JC (19 December 2013). "Uncovering the role of p53 splice variants in human
malignancy: a clinical perspective". OncoTargets and Therapy 7: 57–
68. doi:10.2147/OTT.S53876. PMID 24379683.
• 2 Ziemer MA, Mason A, Carlson DM (1982). "Cell-free translations of proline-rich protein mRNAs". J. Biol.
Chem. 257 (18): 11176–80. PMID 7107651.
• 3 http://www.ncbi.nlm.nih.gov/
• 4. Di Agostino S, Strano S, Emiliozzi V, Zerbini V, Mottolese M, Sacchi A, et al. Gain of function of mutant p53:
the mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation.
Cancer Cell (2006) 10(3):191–202. doi:10.1016/j.ccr.2006.08.013
• 5. Fontemaggi G, Dell’Orso S, Trisciuoglio D, Shay T, Melucci E, Fazi F, et al. The execution of the transcriptional
axis mutant p53, E2F1 and ID4 pro-motes tumor neo-angiogenesis. Nat Struct Mol Biol (2009) 16(10):1086–93.
doi:10.1038/nsmb.1669
• 6. Stambolsky P, Tabach Y, Fontemaggi G, Weisz L, Maor-Aloni R, Siegfried Z, et al. Modulation of the vitamin
D3 response by cancer-associated mutant p53. Cancer Cell (2010) 17(3):273–85. doi:10.1016/j.ccr.2009.11.025
• 7. Do PM, Varanasi L, Fan S, Li C, Kubacka I, Newman V, et al. Mutant p53 cooperates with ETS2 to promote
etoposide resistance. Genes Dev (2012) 26(8):830–45. doi:10.1101/gad.181685.111
• 8. Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, et al. Gain- of-function p53 mutants co-opt
chromatin pathways to drive cancer growth. Nature (2015) 525(7568):206–11. doi:10.1038/nature15251
• 9. Borellini F, Glazer RI. Induction of Sp1-p53 DNA-binding heterocomplexes during granulocyte/macrophage
colony-stimulating factor-dependent proliferation in human erythroleukemia cell line TF-1. J Biol Chem (1993)
268(11):7923–8.
• 10.Sampath J, Sun D, Kidd VJ, Grenet J, Gandhi A, Shapiro LH, et al. Mutant p53 cooperates with ETS and
selectively up-regulates human MDR1 not MRP1. J Biol Chem (2001) 276(42):39359–67.
doi:10.1074/jbc.M103429200

19. Summary
• CANCER Introduction
• Structure of p53
• Function of p53
• Literature Review
• Conclusion

20. Questionnaire

23. Ashish Kumar
ashish.narayan.ashu@gmail.com
9555564734