◀ Back to CCND1
CCND1 — RB1
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
RB1
→
Complex of CCND1-CDK4
(increases, RB1 Activity)
Evidence: The primary substrates of CDK4/6 and CDK2 in G1 progression are the members of the retinoblastoma protein family RB,p107 and p130 The activity of the RB proteins is modulated by sequential phosphorylation by CDK4/6cyclinD and CDK2cyclinE complexes
-
BioCarta p53 signaling pathway:
RB/E2F-1 complex (E2F1-RB1)
→
CDK4/CYCLIN D1/PCNA complex (CDK4-CCND1-PCNA)
(modification, collaborate)
-
BioCarta p53 signaling pathway:
CDK4/CYCLIN D1/PCNA complex (CDK4-CCND1-PCNA)
→
RB (RB1)
(modification, activates)
-
BioCarta influence of ras and rho proteins on g1 to s transition:
CYCLIN D1/CDK4/CDK6 complex (CCND1-CDK4-CDK6)
→
RB/E2F-1 complex (E2F1-RB1)
(modification, activates)
-
BioCarta influence of ras and rho proteins on g1 to s transition:
CYCLIN D1/CDK4/CDK6 complex (CCND1-CDK4-CDK6)
→
RB (RB1)
(modification, activates)
-
BioCarta cell cycle: g1/s check point:
RB/HDAC/ABL/E2F-1/DP-1 complex (E2F1-RB1-TFDP1-ABL1-HDAC1)
→
CYCLIN D1/CDK4/CDK6 complex (CCND1-CDK4-CDK6)
(modification, collaborate)
-
KEGG Cell cycle:
Complex of CCND1-CCND2-CCND3-CDK4-CDK6
→
RB1
(protein-protein, inhibition)
-
KEGG Pathways in cancer:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
KEGG Pancreatic cancer:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
KEGG Glioma:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
KEGG Glioma:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
KEGG Melanoma:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
KEGG Bladder cancer:
Complex of CCND1-CDK4
→
RB1
(protein-protein, activation)
-
KEGG Chronic myeloid leukemia:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
KEGG Small cell lung cancer:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
KEGG Non-small cell lung cancer:
Complex of CCND1-CDK4-CDK6
→
RB1
(protein-protein, activation)
-
NCI Pathway Database Regulation of retinoblastoma protein:
RB1/E2F1-3/DP/HDAC1 complex (RB1-HDAC1-E2F3_E2F2_E2F1-TFDP1)
→
CDK4-6/Cyclin D/p16INK4a complex (CDK6_CDK4-CCND3_CCND2_CCND1-CDKN2A)
(modification, collaborate)
Zhang et al., Cell 2000, Rubin et al., Cell 2005, Kato et al., Genes Dev 1993, Fåhraeus et al., Curr Biol 1996
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Regulation of retinoblastoma protein:
RB1/E2F1-3/DP/HDAC1 complex (RB1-HDAC1-E2F3_E2F2_E2F1-TFDP1)
→
CDK4-6/Cyclin D complex (CDK6_CDK4-CCND3_CCND2_CCND1)
(modification, collaborate)
Zhang et al., Cell 2000, Rubin et al., Cell 2005, Kato et al., Genes Dev 1993, Fåhraeus et al., Curr Biol 1996
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database Regulation of retinoblastoma protein:
RB1/E2F1-3/DP/SUV39H1 complex (RB1-SUV39H1-E2F3_E2F2_E2F1-TFDP1)
→
CDK4-6/Cyclin D complex (CDK6_CDK4-CCND3_CCND2_CCND1)
(modification, collaborate)
Vandel et al., Mol Cell Biol 2001
Evidence: assay
-
NCI Pathway Database FOXM1 transcription factor network:
RB1/FOXM1C complex (FOXM1-RB1)
→
Cyclin D1/CDK4 complex (CCND1-CDK4)
(modification, collaborate)
Wierstra et al., Biol Chem 2006
Evidence: mutant phenotype, reporter gene, physical interaction
-
Reactome Reaction:
RB1
→
CCND1
(reaction)
Connell-Crowley et al., Mol Biol Cell 1997
-
WikiPathways H19 action Rb-E2F1 signaling and CDK-β-catenin activity:
CDK4/CCND1
→
RB1
(activation)
-
WikiPathways Retinoblastoma (RB) in Cancer:
Complex of CDK4-CCND1
→
RB1
(mim-inhibition)
-
WikiPathways Retinoblastoma (RB) in Cancer:
Complex of CDK6-CCND1
→
RB1
(mim-inhibition)
-
WikiPathways Signaling Pathways in Glioblastoma:
Complex of CCND1-CCND2-CDK4
→
RB1
(mim-inhibition)
-
WikiPathways Signaling Pathways in Glioblastoma:
Complex of CCND1-CCND2-CDK6
→
RB1
(mim-inhibition)
-
WikiPathways Bladder Cancer:
CCND1
→
RB1
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Bind Interaction:
CCND1
—
RB1
Siegert et al., Oncogene 2000*
-
IRef Bind_translation Interaction:
CCND1
—
RB1
(affinity chromatography technology)
Siegert et al., Oncogene 2000*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Gaiddon et al., J Biol Chem 2003
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Yarbrough et al., J Natl Cancer Inst 1999*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Zarkowska et al., J Biol Chem 1997*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Nakanishi et al., Biochem Biophys Res Commun 1999*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(physical association, affinity chromatography technology)
Dowdy et al., Cell 1993*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, pull down)
Siegert et al., Oncogene 2000*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(physical association, affinity chromatography technology)
Dasgupta et al., Mol Cell Biol 2004*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, pull down)
Chan et al., Oncogene 2001*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Dasgupta et al., Mol Cell Biol 2004*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Poon et al., J Biol Chem 1996
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Kitagawa et al., EMBO J 1996*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Sweeney et al., Oncogene 1997*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Connell-Crowley et al., Mol Biol Cell 1997
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Musgrove et al., J Cell Biochem 1996*
-
IRef Biogrid Interaction:
CCND1
—
RB1
(direct interaction, enzymatic study)
Higashi et al., Eur J Biochem 1996
-
IRef Hprd Interaction:
Complex of 17 proteins
(in vivo)
Ezhevsky et al., Proc Natl Acad Sci U S A 1997*
-
IRef Hprd Interaction:
CCND1
—
RB1
(in vivo)
Dowdy et al., Cell 1993*
-
IRef Intact Interaction:
Complex of CDK4-CCND1-RB1
(phosphorylation reaction, protein kinase assay)
Fernández et al., Oncogene 2011*
-
IRef Ophid Interaction:
CCND1
—
RB1
(aggregation, confirmational text mining)
Dowdy et al., Cell 1993*
-
IRef Ophid Interaction:
CCND1
—
RB1
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Okami et al., Oncogene 1999
(Carcinoma, Squamous Cell...) :
The phosphorylation of
pRb is
regulated positively by
cyclin D1/CDK4 and negatively by CDK inhibitors, such as p16 ( CDKN2/MTS-1/INK4A )
Liberto et al., Cancer Lett 2000
(Breast Neoplasms) :
EGCG induced p21 ( CIP1/WAF1/SDI1 ),
inhibited cyclin D1-associated pRB kinase activity, and impaired
pRB phosphorylation
Hennigan et al., Mol Biol Cell 2001
:
However,
pRB is hypophosphorylated in GFP-TAM67 arrested cells and the activity of both the
cyclin D1 : cdk and the cyclin E : cdk complexes are
impaired
Cozar-Castellano et al., Diabetes 2004
:
pRb is present in rat and human islets, and overexpression of
cyclin D(1)/cdk-4 led to strikingly enhanced
pRb phosphorylation in both species
Sawant et al., Toxicology 2007
(Carbon Tetrachloride Poisoning...) :
In contrast to the non-DB rats, CCl ( 4 ) administration led to lower plasma IL-6, decreased ERK1/2 activation, lower
cyclin D1 , and cdk 4/6 expression
resulting in decreased
p-pRB and inhibition of liver cell division in the DB rats
Srivastava et al., Cell cycle (Georgetown, Tex.) 2007
(Prostatic Neoplasms) :
The suppression of
cyclin D1 and cyclin E by curcumin may
inhibit CDK mediated phosphorylation of
pRb protein
Guo et al., J Biol Chem 2009
:
Cyclin A,
cyclin D1 , cyclin D2, and Cdk4/6 expression was not
affected by absent
pRb expression
Yang et al., J Infect 2009
(Acute Kidney Injury...) :
Nevertheless, upregulation of
cyclin D1/CDK4 and cyclin E/CDK2
induced pRb phosphorylation, which resulted in the G1/S transition 48 h after CLP
Abcejo et al., Shock 2011
(Sepsis) :
We conclude that 2CLP impaired hepatocyte proliferation following 2CLP in part via impaired
cyclin D1/cdk-4 induced phosphorylation of
pRb , maintaining the association between pRb and E2F and inhibited E2F transcriptional activity
Ikeda et al., Oncol Rep 2013
:
We found that exogenous mutant
cyclin D1 ( T286I ) accumulated in the nuclei in HEK-293T cells, and that
it inhibited the expression
of pRb
Lukas et al., Mol Cell Biol 1995
:
These data provide evidence for an upstream control function of
cyclin D1/cdk4 , and a downstream
role for
pRB , in the order of events regulating transition through late G1 phase of the mammalian cell division cycle
Resnitzky et al., Mol Cell Biol 1995
:
We show here that while premature expression of either cyclin alone advances the G1/S-phase transition to the same extent, premature expression of
cyclin D1 leads to immediate appearance of hyperphosphorylated
pRb , while premature expression of cyclin E does not
Marhin et al., Oncogene 1996
(Cell Transformation, Neoplastic) :
Cyclin D1 can bind and phosphorylate the product ( pRb ) of the retinoblastoma gene ( RB-1 ) and recent evidence suggests
pRb , in turn, may
regulate cyclin D1 protein expression ... In transformed cell lines, loss of
pRb activity strongly correlates with a decrease in cyclin D1 protein expression, and conversely, introduction of pRb can
induce cyclin D1 promoter activity ... We show here that
pRb does not
regulate cyclin D1 directly as basal and serum stimulated levels of cyclin D1 protein and kinase activity are similar in wildtype and pRb-deficient primary mouse embryonic fibroblasts ( MEFs ) ... These observations suggest that the suppression of
cyclin D1 in pRb-minus tumour cell lines
requires both loss of
pRb and at least one additional genetic event
Zukerberg et al., Blood 1996
(Lymphoma, B-Cell...) :
To examine the
effect of
cyclin D1 overexpression on
pRB in primary tumor tissue, we studied pRB expression in low-grade B-cell neoplasms, with particular regard to mantle cell lymphoma, which is characterized by cyclin D1 (bcl-1) overexpression ... Our data from primary lymphoma tissue suggests that overexpression of
cyclin D1 , whereas tumorigenic, does not
lead to
pRB loss or hyperphosporylation
Fåhraeus et al., Curr Biol 1996
:
We have identified a 20-residue synthetic peptide -- corresponding to amino acids 84-103 of p16 -- that interacts with cdk4 and cdk6, and inhibits the in vitro phosphorylation of
pRb mediated by
cdk4-cyclin D1
Musgrove et al., J Cell Biochem 1996
(Breast Neoplasms) :
Inducible expression of
cyclin D1 in T-47D human breast cancer cells is
sufficient for Cdk2 activation and
pRB hyperphosphorylation ... These data show that
cyclin D1 induction is
sufficient for Cdk2 activation and
pRB hyperphosphorylation in T-47D human breast cancer cells, providing evidence that cyclin D1 induction is a critical event in G1 phase progression
Watanabe et al., Mol Cell Biol 1998
:
Overexpression of
pRB activated the
cyclin D1 promoter, and a dominant interfering pRB mutant was defective in cyclin D1 promoter activation