Gene interactions and pathways from curated databases and text-mining

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CCND1 — STAT3

Pathways - manually collected, often from reviews:

  • OpenBEL Selventa BEL large corpus: STAT3 → CCND1 (directlyDecreases, CCND1 Activity)
    Evidence: In coimmunoprecipitation and pull-down assays, cyclin D1 was found to associate with the activation domain of STAT3 upon IL-6 stimulation. Overexpression of cyclin D1 inhibited transcriptional activation by STAT3 proteins, and this effect was again independent of CDK4 kinase activity (114).
  • KEGG Jak-STAT signaling pathway: STAT1/STAT2/STAT3/STAT4/STAT5A/STAT5B/STAT6 → CCND1/CCND2/CCND3 (gene expression, expression)
  • NCI Pathway Database Neurotrophic factor-mediated Trk receptor signaling: STAT3 (dimer) complex (STAT3) → Cyclin D1 (CCND1) (transcription, activates) Ng et al., J Biol Chem 2006*
    Evidence: mutant phenotype, other species

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Bienvenu et al., J Biol Chem 2001 : In this study, we show that cyclin D1 inhibits STAT3 activation ... Whereas cyclin D1 had no effect on the steady-state level of STAT3 proteins in the cytoplasm, it was found to reduce the STAT3 nuclear level in HepG2 cells
Masuda et al., Cancer Res 2002 (Carcinoma, Squamous Cell...) : In view of the fact that signal transducers and activators of transcription 3 ( Stat3 ) is often activated in HNSCC cells, we examined the effects of Stat3 on cyclin D1 expression and cell proliferation in the YCU-H891 HNSCC cell line that displays constitutive activation of Stat3 ... This study provides the first evidence that in HNSCC, constitutive activation of Stat3 plays a causative role in overexpression of cyclin D1 , and in clinical studies, Stat3 activation may provide a novel prognostic factor
Torbenson et al., Am J Pathol 2002 (Fatty Liver) : Moreover, a striking inverse correlation was noted between hepatocyte nuclear accumulation of phospho-STAT-3 and DNA synthesis ( as assessed by bromodeoxyuridine labeling ), as well as cyclin D1 mRNA induction and protein expression
Matsui et al., J Biol Chem 2002 : Activation of STAT3 in fetal hepatocytes of transgenic mice expressing the STAT3-estrogen receptor fusion protein by 4-hydroxytamoxifen resulted in the suppression of cyclin D1 and D2 expression ... Furthermore, STAT3-C , a constitutively active form of STAT3, suppressed transcription of the cyclin D1 promoter in fetal hepatocytes, whereas it activated the transcription in hepatic tumor cells, huH7 and HepG2
Quintanilla-Martinez et al., Am J Pathol 2003 (Multiple Myeloma) : The study aim was to investigate Stat 3 activation in a series of multiple myeloma ( MM ) cases and its effect on downstream targets such as the anti-apoptotic proteins Bcl-xL, Mcl-1, and Bcl-2, and the cell-cycle protein cyclin D1
Debidda et al., J Biol Chem 2005 (Inflammation) : STAT3 was required for the RhoA induced NF-kappaB and cyclin D1 transcription and was involved in NF-kappaB nuclear translocation
Ng et al., J Biol Chem 2006 : Furthermore, reduced STAT3 expression in PC12 cells suppressed NGF induced cyclin D1 expression, thereby inhibiting growth arrest normally triggered by NGF treatment
Ishii et al., J Natl Cancer Inst 2006 (Breast Neoplasms) : In HBL100 and T47D parental and cyclin D1-overexpressing cells, cyclin D1 overexpression was also inversely associated with STAT3 expression, and cyclin D1 directly reduced the expression of STAT3
Lu et al., J Biol Chem 2006 : Not only the up-regulation of p50alpha and p55alpha but also the repression of cyclin D1 and Bcl-2 in SOCS3 ( -/- ) MEFs was inhibited by dominant negative STAT3
Wang et al., Circ Res 2007 (Carotid Artery Injuries...) : IL-6 also induced cyclin D1 expression in a time- and gp130/STAT-3 dependent manner in VSMCs. Suppression of cyclin D1 levels via the use of its small interfering RNA molecules inhibited IL-6 induced VSMC motility ... Blockade of gp130/STAT-3 signaling via adenovirus mediated expression of dngp130 or dnSTAT-3 attenuated balloon injury induced STAT-3 phosphorylation and cyclin D1 induction , resulting in reduced smooth muscle cell migration from media to intima and decreased neointima formation
Ishii et al., Cancer Res 2008 (Breast Neoplasms) : We show that repression of STAT3 by cyclin D1 inhibits cell growth on Matrigel and in tumors in vivo ; however, treatment with tamoxifen abolishes cyclin D1-mediated repression of STAT3 and growth suppression
Delgado et al., Dig Dis Sci 2008 (Adenocarcinoma...) : This drug significantly reduced the up-regulations of cyclin D1 , cyclin E, c-Myc, and Bcl-2 as well as the activation of STAT3 in SEG-1 cells
Won et al., Anticancer Res 2010 (Carcinoma, Hepatocellular...) : Moreover, overexpression of constitutively active STAT3 increased cyclin D1 transcriptional activity and protein expression, whereas overexpression of a dominant negative STAT3 deletion mutant ( STAT3 ( 1-588 ) ) reduced cyclin D1 transcriptional activity
Suzuki et al., J Surg Res 2012 (Ischemia) : Liver mass restoration was significantly retarded in the old rats, despite higher plasma IL-6 levels, rapid and prolonged activation of hepatic STAT3 , and increased hepatocyte nuclear cyclin D1 levels
Kim et al., Carcinogenesis 2011 (Breast Neoplasms...) : These results indicate that Stat3 plays an important role in BITC mediated inhibition of leptin induced cyclin D1 transactivation
Guo et al., PloS one 2011 : Mechanistic characterization revealed that NSC-743380 suppressed the phosphorylation of C-terminal domain of RNA polymerase II, induced JNK activation, inhibited JAK2/STAT3 phosphorylation and suppressed cyclin D1 expression in sensitive human cancer cells
Sun et al., Journal of translational medicine 2012 : Down regulation of STAT-3 with siRNA resulted in a reduced expression of Bcl-2 and cyclin D1
Li et al., PloS one 2012 : Pharmacological inhibition of JAK/STAT3 , PI3K/Akt or MEK/ERK signaling by AG490, Wortmannin or U0126, respectively, reduced leptin induced cyclin D1 expression and NP cell proliferation
Tkach et al., Endocr Relat Cancer 2013 (Breast Neoplasms) : Expression of a Stat3S727A vector, which carries a serine-to-alanine substitution at codon 727, shows that Stat3Ser727 phosphorylation is required for full transcriptional activation of cyclin D1 gene expression by progestins and for in vivo Stat3 recruitment on cyclin D1 promoter