CW December 2001

category image Volume 10
Issue Number 12
December 2001
ISSN 10593802

p53 Function: A Sidebar

p53 is the guardian of the genome, and induces
potentially cancerous cells to commit suicide. In this issue of Cancer Watch, the articles "Drug Resistance in Neuroblastoma" and "News in Brief" deals with the involvement of p53. Hence a short description of the basics of p53 is given below.
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Binding of p53 to DNA. The p53 tetramer (shown in gold, blue, green and magenta) binds to DNA (in silver at bottom) and causes the expression of the p21 proteiin.

p53 is a tumor suppressor protein which modulates cell cycle and induces potentially cancerous cells to commit suicide.

When cellular DNA is damaged, p53 gene is activated, resulting in the production of p53 protein which binds to DNA causing the expression of the p21 gene. Now p21 protein is produced whic h has two roles.

It inhibits the proteins cyclin dependent kinases (Cdk2-cyclin E) which are necessary for the passage of cells from G1 to the DNA synthesis (S) phase in the cell cycle. Thus p21 protein prevents the G1 to S passage in the cell cycle. This is G1 arrrest.

If the cells were already in the S phase, p21 will block the activity of a small nuclear protein PCNA (Proliferating Cell Nuclear Antigen) involved in DNA replication and repair in cells.

Thus p53 unleashes cascading events via p21 to shut down cell cycle and initiate cell suicide as shown below.

Source & Additional Reading

S. R. Durell et al., in Structure, Motion, Interaction and Expression of Biological Macromolecules, p. 277-295, Eds., R. H. Sarma & M. H. Sarma, Adenine Press (1998).

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