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P53 role in apoptosis

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Moataz Mohamed

on 11 December 2013

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Transcript of P53 role in apoptosis

P53 role in Apoptosis
What is Apoptosis?
Apoptosis :
is the process of programmed cell death (PCD)

The Apoptotis is mainly occur by 3 steps :
1) Initiation 2)Execution 3)Phagosytosis

-
Initiation
:
A)Intrinsic Pathway of initiation (Mitochondrial Apoptosis)
B)Extrinsic Pathway of initiation (Death Receptor Apoptosis)

In both pathways, caspases are activated to cleave cellular substrates

-
Capspases -
a family of cysteine-rich proteases
-
is the main executioner of apoptosis.
1- Transcriptional-dependent mechanisms
P53, The guardian of the genome
The P53, also known as TP53 or tumor protein was discovered 34 years ago.
(oren M. ,1999)
P53 is now known to be the product of a major tumor suppressor gene that is the most common target for genetic alterations in human cancer. (50-60% of cancers has
P53
mutations).
(Greenblatt et al.;1994)
P53 is mainly a sequence-specific transcription factor that is kept at low levels in healthy cells.
The genes regulated by the p53 protein form the p53 pathway can result in cell cycle arrest, apoptosis and cell senescence.
(Amaral et al .;2010)

P53 can regulate apoptosis through different mechanisms:
1- Transcriptional-dependent mechanisms
2- Transcription-independent mechanisms
(Moll et al., 2005)

2- Transcriptional-independent mechanisms
Recent studies have discovered that P53 has role in apoptosis by other ways rather than transcriptional pathway two mechanism has been described for transcriptional independent pathway of P53 in apoptosis.

A. through induce permeabilization of OMM.

B. The second mechanism is through the activation of BAX

(Moll et al., 2005)


P53 Regulation
A key player in the regulation of P53 is the MDM2 protein.
The binding of MDM2 to P53 promotes the ubquitination of p53 and promote degredation by the proteasome A.


Some molecules regulate P53/MDM2 loop:
OTU5 , caveolin & Nutlin-3

(Lou.J. et al.;2013), (Liu & Xu ,2011)

Remember That
P53
is a tumor suppressor gene while
MDM2
is an oncogene.
either mutation in P53 or increased MDM2 could lead to cancer.
The END

Thanks
http://www.biooncology.com/research-education/apoptosis/pathways
http://www.cgl.ucsf.edu/chimera/ImageGallery/entries/p53/p53ambient.html
(Amaral et al.;2010)
(Oren M. ,1999)
(image adopted from youtube)
(oren M. ,1999)
(Hanhan&Weinberg ,2011)
Special Thanks to Dr Shaimaa
Full transcript