Question

Describe how pRB controls passage of cells through the restriction point. Include in your answer a description of the molecules that modify pRB function. Identify three mechanisms cancer cells can use to distrupt control of RB function.

Answer 1

The retinoblastoma protein is a tumor supressor protein that is dysfunctional in several major cancers. One function of pRB is to prevent excessive cell growth by inhibiting cell cycle progression untila a cell is ready to divide. Now let's check how pRB controlspassage of cell through restriction point:

Consider Cyclin D bound cdk s 4 and 6 are activated by cdk-activating kinase and drive the cell towards the restriction point. Active cyclin D-cdk complexes phosphorylate retinoblastoma protein (pRb) in the nucleus. Unphosphorylated Rb acts as an inhibitor of G1 by preventing E2F- mediated transcription.

active G-Cdk positive feedback active Rb protein active G/S-Cdk active E2F protein S-phase gene transcription GS. cyclin (cyclin E) S-cyclin Icyclin A) active S.cdk DNA SYNTHESIS inactivated E2F protein P positive feedback inactivated Rb protein