Identifiers
cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)
HUGO:CDKN2B, HGNC:1788, ENTREZ:1030, GENECARDS:GC09M021992, UNIPROT:P42772

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
 EMT Senescence   / EMT_REGULATORS 
 EMT Senescence   / SENESCENCE 

References
PMID:11013220
Cooperation and physical interaction of Smad2, Smad3, Smad4 with SP1 at the promoter of CDKN2B (p15INK4B) gene
This interaction provides a mechanism underlying the TGFB-induced growth arrest
PMID:10331086
CDK inhibitors are classified into 2 families: Cip/Kip family and INK4 family
INK4 family consists of p16INK4a, p15INK4B, p18INK4c, p19INK4d
INK4 family spcially interacts with Cdk4 and Cdk6 but not other Cdks
INK4 binding prevents the association of Cdk4 and Cdk6 with the D-type cyclins (D1, D2, D3)
The vast majority of INK4 proteins are not found in complexes containing cyclins D.
PMID:8078588
p15INK4B is a potential effector of TGFB-induced cell cycle arrest
PMID:22943793
TGFB induces expression of p15INK4B and represses expression of c-Myc
p15INK4B is able to prevent cyclin D-CDK4/6 complex formation
p15INK4B displaces p21CIP and p27KIP1 from cyclin D-CDK4/6 complexes.
These CIP/KIP inhibitors are subsequently able to inactivate other complexes of G1 and S phase and therby inhibit cell cycle.
PMID:23140366
PMID:17055429
p16 and p15 activates the pRB tumor supressor by inhibiting the cyclin dependent kinase CDK4 and CDK6, which promotes proliferation. The inhibition of CDK4 and CDK6 ability to phosphorylate Rb, maintains Rb-family protein in a hypophosphorylated state which promotes G1 cell cycle arrest

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
 EMT Senescence   / EMT_REGULATORS 

References
PMID:11013220
Cooperation and physical interaction of Smad2, Smad3, Smad4 with SP1 at the promoter of CDKN2B (p15INK4B) gene
This interaction provides a mechanism underlying the TGFB-induced growth arrest
PMID:10331086
CDK inhibitors are classified into 2 families: Cip/Kip family and INK4 family
INK4 family consists of p16INK4a, p15INK4B, p18INK4c, p19INK4d
INK4 family spcially interacts with Cdk4 and Cdk6 but not other Cdks
INK4 binding prevents the association of Cdk4 and Cdk6 with the D-type cyclins (D1, D2, D3)
The vast majority of INK4 proteins are not found in complexes containing cyclins D.
PMID:8078588
p15INK4B is a potential effector of TGFB-induced cell cycle arrest
PMID:22943793
TGFB induces expression of p15INK4B and represses expression of c-Myc
p15INK4B is able to prevent cyclin D-CDK4/6 complex formation
p15INK4B displaces p21CIP and p27KIP1 from cyclin D-CDK4/6 complexes.
These CIP/KIP inhibitors are subsequently able to inactivate other complexes of G1 and S phase and therby inhibit cell cycle.
em_emtc_emtc_re256( EMT Senescence  ):
PMID:23140366
PMID:17055429
p16 and p15 activates the pRB tumor supressor by inhibiting the cyclin dependent kinase CDK4 and CDK6, which promotes proliferation. The inhibition of CDK4 and CDK6 ability to phosphorylate Rb, maintains Rb-family protein in a hypophosphorylated state which promotes G1 cell cycle arrest

1. p15INK4B*@Cytosol

1. CDK4_6*:​p15INK4B*@Cytosol

1. rp15INK4B*@Nucleus → p15INK4B*@Cytosol
2. CDK4_6*@Cytosol + p15INK4B*@Cytosol → CDK4_6*:​p15INK4B*@Cytosol