P-TEFb is degraded by Siah1/2 in quiescent cells-Huang etc

P-TEFb, composed of CycT1 and CDK9, regulates the elongation of
transcription by RNA polymerase II. In proliferating cells, it is
regulated by 7SK snRNA in the 7SK snRNP complex. In resting cells, P-TEFb
is absent, because CycT1 is dephosphorylated, released from CDK9 and
rapidly degraded. In this study, we identified the mechanism of this
degradation. We mapped the ubiquitination and degradation of free CycT1 to
its N-terminal region from positions 1 to 280. This region is
ubiquitinated at six lysines, where E3 ligases Siah1 and Siah2 bind and
degrade these sequences. Importantly, the inhibition of Siah1/2 rescued
the expression of free CycT1 in proliferating as well as resting primary
cells. We conclude that Siah1/2 are the E3 ligases that bind and degrade
the dissociated CycT1 in resting, terminally differentiated, anergic
and/or exhausted cells.