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)
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.
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
e_re280( EMT ):
A Myc–Miz-1 complex binds to the p15 promoter
Miz1: a Myc-interacting Zinc-finger protein that recognizes certain transcriptional initiator elements
One of this transcriptional initiator element contains the sequence 5′-CCCACTCTGC corresponding to the p15INK4B transcriptional intiator
e_re275( EMT ):
-Smad4 transactivated the proximal p21 promoter 1.3-fold
-Smad2 transactivated the proximal p21 promoter 3-fold
-Smad2/4 transactivated the proximal p21 promoter 12-fold
-Smad3 transactivated the proximal p21 promoter 25-fold
-Smad3/Smad2 transactivated the proximal p21 promoter 40-fold
-Smad3/Smad4 transactivated the proximal p21 promoter 110-fold
-Smad2/Smad3/Smad4 transactivated the proximal p21 promoter 140-fold
Smad proteins act as Transcriptional Activators via functional interactions with the Transcription factor Sp1
Myc represses differentiation-induced p21 expression via Miz-1-dependent interaction with the p21 core promoter
Myc binds the p21 core promoter in vitro through interaction with Miz-1
Myc and Miz-1 interact with the p21 promoter in vivo
Snail regulates cell-cycle progression and survival:
Snail regulates components of the early to late G1 transition and the G1/S checkpoint.
Snail represses Cyclin D2 transcription and increases p21/Cip1 transcription.
SNAI2 induces p21CIP1 (CDKN1A) expression
Participates in complexes:
In compartment: Nucleus
Participates in reactions:
As Reactant or Product: