Search results for CCNC

Showing 11 results out of 11

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Species

Types

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Protein (1 results from a total of 1)

Identifier: R-HSA-212418
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: CCNC: P24863

Complex (4 results from a total of 4)

Identifier: R-HSA-1604465
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-1604463
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-NUL-2064914
Species: Xenopus laevis, Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-2220980
Species: Homo sapiens
Compartment: nucleoplasm

Set (1 results from a total of 1)

Identifier: R-HSA-2176485
Species: Homo sapiens
Compartment: nucleoplasm

Reaction (4 results from a total of 4)

Identifier: R-NUL-2064916
Species: Homo sapiens, Xenopus laevis
Compartment: nucleoplasm
Recruitment of CDK8 and cyclin C (CDK8:CCNC) by MAML, a constituent of the NOTCH1 coactivator complex, was studied in HeLa cells in which tagged human MAML, CDK8 and CCNC proteins were expressed together with a tagged Xenopus NICD1 (xNICD1).
Identifier: R-HSA-2220957
Species: Homo sapiens
Compartment: nucleoplasm
MAML is expected to recruit CDK8 to NICD1 PEST domain mutants like it recruits CDK8 to wild-type NICD1 (Fryer et al. 2004).
Identifier: R-NUL-2065178
Species: Homo sapiens, Xenopus laevis
Compartment: nucleoplasm
TAD and PEST domains of NOTCH intracellular domain contain multiple conserved cyclin-dependent kinase phosphorylation sites. In vitro, recombinant human CDK8 in complex with recombinant human cyclin C (CDK8:CCNC) readily phosphorylates recombinant Xenopus NICD1 (xNICD1). This phosphorylation also occurs when these recombinant proteins are expressed in HeLa cells, and was directly shown to involve conserved serine residues in the PEST domain. Phosphorylation by CDK8 targets xNICD1 for ubiquitination and subsequent degradation, thereby coordinating NICD1 transcriptional activity with NICD1 turnover.
Identifier: R-HSA-2176475
Species: Homo sapiens
Compartment: nucleoplasm
CDK8 in complex with cyclin C (CDK8:CCNC) and CDK9 in complex with cyclin T (CDK9:CCNT) are able to phosphorylate the linker region of SMAD2 and SMAD3. In SMAD3, CDK8/CDK9 preferentially targets threonine residue T179, although serine residues S208 and S213 can also be phosphorylated. In SMAD2, CDK8/9 preferentially targets threonine residue T220 (corresponds to T190 in the short isoform of SMAD2, SMAD2-2). Phosphorylation of serine residues that correspond to serines S208 and S213 of SMAD3 has not been examined. Phosphorylation of the linker region of SMAD2 and SMAD3 by CDK8/CDK9 enhances transcriptional activity of SMAD2/3:SMAD4 complex, but also primes SMAD2 and SMAD3 for ubiquitination and subsequent degradation (Alarcon et al. 2009).

Pathway (1 results from a total of 1)

Identifier: R-HSA-2173796
Species: Homo sapiens
After phosphorylated SMAD2 and/or SMAD3 form a heterotrimer with SMAD4, SMAD2/3:SMAD4 complex translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003). In the nucleus, linker regions of SMAD2 and SMAD3 within SMAD2/3:SMAD4 complex can be phosphorylated by CDK8 associated with cyclin C (CDK8:CCNC) or CDK9 associated with cyclin T (CDK9:CCNT). CDK8/CDK9-mediated phosphorylation of SMAD2/3 enhances transcriptional activity of SMAD2/3:SMAD4 complex, but also primes it for ubiquitination and consequent degradation (Alarcon et al. 2009).

The transfer of SMAD2/3:SMAD4 complex to the nucleus can be assisted by other proteins, such as WWTR1. In human embryonic cells, WWTR1 (TAZ) binds SMAD2/3:SMAD4 heterotrimer and mediates TGF-beta-dependent nuclear accumulation of SMAD2/3:SMAD4. The complex of WWTR1 and SMAD2/3:SMAD4 binds promoters of SMAD7 and SERPINE1 (PAI-1 i.e. plasminogen activator inhibitor 1) genes and stimulates their transcription (Varelas et al. 2008). Stimulation of SMAD7 transcription by SMAD2/3:SMAD4 represents a negative feedback loop in TGF-beta receptor signaling. SMAD7 can be downregulated by RNF111 ubiquitin ligase (Arkadia), which binds and ubiquitinates SMAD7, targeting it for degradation (Koinuma et al. 2003).

SMAD2/3:SMAD4 heterotrimer also binds the complex of RBL1 (p107), E2F4/5 and TFDP1/2 (DP1/2). The resulting complex binds MYC promoter and inhibits MYC transcription. Inhibition of MYC transcription contributes to anti-proliferative effect of TGF-beta (Chen et al. 2002). SMAD2/3:SMAD4 heterotrimer also associates with transcription factor SP1. SMAD2/3:SMAD4:SP1 complex stimulates transcription of a CDK inhibitor CDKN2B (p15-INK4B), also contributing to the anti-proliferative effect of TGF-beta (Feng et al. 2000).

MEN1 (menin), a transcription factor tumor suppressor mutated in a familial cancer syndrome multiple endocrine neoplasia type 1, forms a complex with SMAD2/3:SMAD4 heterotrimer, but transcriptional targets of SMAD2/3:SMAD4:MEN1 have not been elucidated (Kaji et al. 2001, Sowa et al. 2004, Canaff et al. 2012).

JUNB is also an established transcriptional target of SMAD2/3:SMAD4 complex (Wong et al. 1999).
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