→ rp15INK4B*@Nucleus References
PMID:11283613
Miz-1 regulates expression of p15INK4b
The Myc/Miz1 complex binds to the p15 promoter
Myc inhibits binding of p300 to Miz-1
Myc inhibits expression of p15INK4B by binding to Miz-1 (Myc represses p15INK4B by interacting with Miz1)
PMID:11283614
Disruption of the Myc-Miz1 interaction prevents repression of p15INK4B by Myc.
TGFB relieves Myc-mediated repression of p15INK4B by downregulating Myc bound to the p15INK4B transcriptional initiator region.
At the same time TGFB induces the formation of a Smad transcriptional complex that recognizes the p15INK4B promoter.
Is is proposed that by relieving the Myc-mediated repression of p15INK4B, TGFB allows this gene to be activated by the Smad complex.
TGFB signaling controls p15INK4B activation by 2 coupled events: transactivation and relief of repression.
PMID:10454538
Myc prevents inhibition of G1 CDKs by TGFB.
Inhibition of the p15 promoter by c-Myc.
Enforced expression of Myc abrogates p15INK4B induction and CDK inhibition by TGFB
Myc downregulation by TGFB is required for Activation of the p15Ink4b G1 Arrest Pathway
3 populations of endogenous CDK4: Latent pools (400 kDa, source of CDK4 for Cyclin D), Active CDK4-CyclinD complex, Inactive monomeric CDK4