Modulators and effectors of RB protein (pRB) functions. DNA damage induces phosphorylation of pRB by ATM and Chk1/2, whereas oxidative stress induces dephosphorylation of pRB through PP2A. AMP‐activated kinase (AMPK) also phosphorylates pRB. pRB is acetylated by p300, PCAF, methylated by Set 7/9 and SMYD, and degradaded via MDM2‐mediated ubiquitination and caspase 3 and 8 activation. Several molecules, Skp2, KDM5A and EID1, are activated after dissociation from pRB in an E2F‐independent manner. Released Skp2 promotes ubiquitination and degradation of phospho‐p27kip1.