CyclinD1*

RNA CyclinD1* map

Identifiers
cyclin D1
HUGO:CCND1 HGNC:1582 ENTREZ:595 UNIPROT:P24385 GENECARDS:CCND1 REACTOME:68327 KEGG:595 ATLASONC:BCL1 WIKI:CCND1

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Apoptosis  map  / APOPTOSIS_GENES  map

References
PMID:19238148
CDK activity requires binding of regulatory subunits known as cyclins.
Cyclins are synthesized and destroyed at specific times during the cell cycle, thus regulating kinase activity in a timely manner.
Human cells contain multiple loci encoding CDKs and cyclins (13 and 25 loci, respectively).
A subset of CDK–cyclin complexes is directly involved in driving the cell cycle:
-3 interphase CDKs (CDK2, CDK4 and CDK6), 1 mitotic CDK (CDK1)
-10 cyclins that belong to 4 different classes (the A-, B-, D- and E-type cyclins).
PMID:9832503
D-type cyclins are labile proteins guarantees
Phosphorylation of cyclin D1 on T286 by GSK3B leads to the rapid ubiquitination and proteasomal degradation of cyclin D1
cyclin D1 accumulates in the nucleus during G1 phase and exits into the cytoplasm during S phase
GSK3B is predominantly cytoplasmic during G1 phase, but a significant fraction enters the nucleus during S phase.
Phosphorylation and proteolytic turnover of cyclin D1 and its subcellular localization during the cell division cycle are linked through the action of GSK3B.
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: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.

rCyclinD1*@Nucleus

References
e_re264( EMT  map ):
PMID:15810077
Beta-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis.
PMID:19020303
When Wnt binds its receptor, Frizzled, beta-catenin is released to translocate from the cytoplasm to the nucleus, where it forms a complex with TCF and/or LEF transcription factors and stimulates cyclin D1 gene transcription
(Beta-catenin/TCF)- mediated cyclin D1 gene transcription is further regulated by active Rac signaling, phosphorylation by protein kinase A (PKA)
PMID:10318916
The cyclin D1 gene is a direct target for transactivation by the beta-catenin/LEF-1 pathway through a LEF-1 binding site in the cyclin D1 promoter.
PMID:10201372
beta-catenin activates transcription from the cyclin D1 promoter, and that sequences within the promoter that are related to consensus TCF/LEF-binding sites are necessary for activation
PMID:14712077
PMID:12663502
Cyclin D1 over-expression correlates with beta-catenin activation
PMID:15377999
Rac1-GTP augments nuclear accumulation of b-catenin and physical association of Rac1 with b-catenin and/or TCF-4 may facilitate this process.
This culminates in the amplification of b-catenin signaling activity, resulting in enhanced transcriptional activation of perhaps a specific subset of Wnt target genes important in cancer progression.


Modifications:
In compartment: Nucleus
  1. rCyclinD1*@Nucleus map

Participates in complexes:

    Participates in reactions:
    As Reactant or Product:

    1. gCyclinD1*@Nucleus map map rCyclinD1*@Nucleus map

    2. rCyclinD1*@Nucleus map map CyclinD1*@Nucleus map
    3. gCyclinD1*@Nucleus map map rCyclinD1*@Nucleus map
    4. rCyclinD1*@Nucleus map map CyclinD1*@Cytoplasm map

    As Catalyser:

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