This document summarizes two important tumor suppressor genes - PRB and P53. It provides background on tumor suppressor genes, noting that they function through loss of function to regulate cell cycle and suppress uncontrolled cell proliferation. For PRB, it describes its role in retinoblastoma cancer and cell cycle regulation. For P53, it discusses its role as the "guardian of the genome" in DNA repair and apoptosis, as well as its structure and functions in halting the cell cycle when damage is detected.

1. TUMOR SUPPRESSOR GENE :
PRB AND P53 GENE
By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )

2. SYNOPSIS
 Introduction
 Tumor Suppressor Gene (TSG)
 History & types of mutation of TSG
 Examples of TSG
 [1] Prb – Retinoblastoma gene:
Structure, Function & Action
 [2] p53-Gene:
Structure ,function & Action
Conclusion
References

3. INTRODUCTION
 Two categories of gene triggers carcinogenesis
 Oncogenes =gain of function
 Tumor Suppressor Gene(TSG) = loss of function
 TSG regulate cell cycle
Definition : “ Genes that suppress the development of
cancer”

4. TRANSFORMED CELL
A: NORMAL CELL ,B: TRANSFORMED CELL

5. HISTORY
 In 1960 by Henry Harris
 fuse normal cell with cancer cell
 Contained gene product
 Suppress uncontrolled cell proliferation

6. FUNCTIONS OF TSG
 Suppress oncogenes
 cell cycle
 Promote apoptosis
 Coupling the cell cycle to DNA damage
 Induce DNA repair

7. THE RAS MAPK( MITOGEN ACTIVATED PROT. KINASE) PATHWAY
CHAIN OF EVENTS

8. MECHANISMS OF FUNCTIONAL TUMOR SUPPRESSOR
LOSS
 Chromosomal aberration : reciprocal
translocation.
 Constitutional chromosomal aberration : deletion
and aneuploidy.
 Interaction of viral oncoproteins & tumor
suppresssor gene : interaction.

9. EXAMPLES OF TSG
Retinoblastoma P53(GUARDIAN OF GENOME)

10. PRB- INTRODUCTION AND HISTORY
 It is first tumor suppressor gene studied.
 Childhood cancer.
 Cause cancer in the retina of the eye.
 Gene responsible for this disorder is named RB.

11. HISTORY AND TYPES OF PRB
 HISTORY-
 In 1971 by Alfred Knudson(University of Texas).
 “Two-hits” hypothesis.
 TYPES-
 Familial Retinoblastoma.
 Sporadic Retinoblastoma.

13. STRUCTURE

14. FUNCTION OF RETINOBLASTOMA GENE
 In cell cycle regulation.
 Passage of cells from G1 to S – phase.
 During which DNA synthesis occurs.

15. ROLE OF PRB IN REGULATING THE CELL CYCLE

17. P53 INTRODUCTION & HISTORY
INTRODUCTION :- P53
 Guardian of the genome.
 Encoded by tp53 gene.
 Involved in all 50% cancer.
HISTORY :-
 In 1989 Bert Vogelstein( John Hopkins school of
medicine).
 SV-40 transformed cells in association with T-
Antigen.

18. STRUCTURE

19. FUNCTIONS & ACTION
 Its activate transcriptional regulator.
 Its halts the cell-cycle until damage is repaired.
 Gene p53 induces apoptosis , senescence , cell-cycle check point arrest ,
DNA repair.
 Somatic mutation
 Ability to Cell cycle arrest.
 ACTION
 Affects cell cycle
 Trapping of p53 protein by an oncogene ( MDM2).
 Cytoplasm localization


20. P53 PROTEIN IS EITHER DEGRADED OR CONVERTED TO P53-P
WHICH
TRIGGERS: 1) CELL CYCLE ARREST FOR DNA REPAIR OR; (2) IF
DNA IS NOT
REPAIRED THEN PROMOTES APOPTOSIS

21. CONCLUSION
TSG are a second class of genes which plays an
important role in tumorigenesis. TSG were
discovered through their association with rare,
inherited cancers such as retinoblastoma.
Mutational inactivation of tumor suppressor
genes is characteristic of most form of cancer.

22. REFERENCES
 Bruce Albert, Alexander Johnson, Julian Lewis,
Martin raff, Keith Roberts, Peter Walter (2002)
Molecular biology of the cell fifth edition published
by Garland science, Taylor and Francis group.
 Gerald karp (1996,1999) Cell and Molecular
Biology Concepts and Experiment Second Edition
published by John wiley and Sonc.Inc.
 Harvey Lodish, Arnold Berk, Paul Matsurdaria,
Chris A.Kaiser, Monty Krieger, Matthew, P.Scott,
S.Lawrence, Zipursky, James Darnell
(1986,1990,1995,2000,2004) Published by W.W.
Freeman and Company.