p53 has been described as “GUARDIAN ANGEL OF THE GENOME” because it performs following mechanism: DNA Repair Cell growth arrest Apoptosis (programmed cell death) P53 is also known as cellular tumour antigen Ag, phosphoprotein P53 or tumour suppressor p53. P53 protein is encoded by TP53.

1. p53
“Guardian
angel of
the
GENOME”

2. CONTENTS

3. p53 has been described as “GUARDIAN ANGEL OF THE GENOME”
because it performs following mechanism:
o DNA Repair
oCell growth arrest
oApoptosis (programmed cell death)
P53 is also known as cellular tumour antigen Ag, phosphoprotein
P53 or tumour suppressor p53.
P53 protein is encoded by TP53.

4.  Molecular weight of p53 is 53.7 kD
The tumor suppressor p53 is a phosphoprotein barely detectable in
the nucleus of normal cells.
The complexity of the p53 response makes this an ideal
system for application of newly emerging rapid throughput
analysis techniques and informatics analysis.

5.  Identified in 1979 by Lionel Crawford, David P. Lane, Arnold Levine &
Llyod Old.
The TP53 gene from mouse was first cloned by Peter Chumakov in 1982.
 Bert Vogelstein working at Johns Hopkins School of Medicine, in 1989, first
revealed the P53 character as a “tumour suppressor gene”.
 Waren Maltzman from Waksman Inst. Of Rulgers University, demonstrated
that TP53 was resposive to DNA damage in the form of ultraviolet radiation.
 In the series of 1991-1992, Michael Kastan, Johns Hopkins university,
reported that TP53 was a critical part of signal transduction pathway that
helped cells respond to DNA damage.
 In 1992, Wafik-El-Deiry with Berk Vogelstein identified the consensus
sequence.

6.  In 1993 P53 was voted as “Molecule Of the year” by Sccience Magazine.
 IN th same year, 1993, Wafik-El-Deiry diiscovered P21(WAF-21) as a gene
regulated by P53.

7. Structure & Function

8. P53 has seven domains :
•N-terminus transcription activation domain (TAD) also known as Activation domain -1
(AD-1) .
N-terminus contains two complementary TAD with major one at residue 1- 42 and a
minor one at residues 55 – 75, specifically involved in the regulation of several
pro-apoptotic genes.
• Activation Domain-2 (AD-2) important for apoptotic activity lies at residue 44-63.
• Proline rich domain important for the apoptotic activity of P-53 (64-92 residues).
• Central DNA binding domain (DBD) contains one Zinc atom and several arginine
amino-acid (102-292). This region is responsible for binding the P-53 co-repressor
LMO3.
• Nuclear localization signalling domain (NLS) (316-325).
• Homo-oligomerisation domain (OD) .Tetramerisation is essential for the activity of P53
in-vivo.
• C-terminal involved in the downregulation of the DNA binding of the central domain
(356-393).

10. P53 AS A TUMOUR SUPPRESSOR

11. P53 REGULATION

12. P53 PATHWAY

14. Role In Disease
•If the TP53 gene is damaged, tumor suppression is severely reduced. People
who inherit only one functional copy of the TP53 gene will most likely
develop tumors in early adulthood, a disorder known as Li-Fraumeni
syndrome.
•Certain pathogens can also affect 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, in
synergy with the inactivation of another cell cycle regulator, pRb, by the
HPV protein E7, allows for repeated cell division manifested in the clinical
disease of warts.
•In healthy humans, the p53 protein is continually produced and degraded
in the cell. The degradation of the p53 protein is, as mentioned, associated
with MDM2 binding. In a negative feedback loop, MDM2 is itself induced
by the p53 protein.

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