CHUK

Protein CHUK map

Identifiers
conserved helix-loop-helix ubiquitous kinase
TCF16
HUGO:CHUK HGNC:1974 ENTREZ:1147 UNIPROT:O15111 GENECARDS:CHUK REACTOME:57214 KEGG:1147 ATLASONC:GC_CHUK WIKI:CHUK

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 EMT  map  / CELL_CELL_ADHESIONS  map
 EMT  map  / ADHERENS_JUNCTIONS  map
 Apoptosis  map  / TNF_RESPONSE  map

References
PMID:12799363
CTNNB1 can be phosphorylated by CHUK (inhibitor of NF fappa-B) at S45, independent of CSNKA1
synonym:IKBKA synonym:IKK_alpha_

CHUK@Cytoplasm

References
e_re464( EMT  map ):
CSNK1 (casein kinase 1) but not CSNK2 (casein kinase 2) phosphorylates CTNNB1 at S45.
This priming phosphorylation results in subsequent phosphorylation by GSK3B at T41, S37, S33.
CTNNB1 that is phosphorylated at S33 and S37 is ultimately recognized by E3-ligase and targeted for proteasomal destruction.
PMID:7542250
Whereas in the normal cells CTNNB1 (beta-catenin) is found in association with E-cadherin, p120 Cas is not. In the ras-transformed cells, the situation is reversed; tyrosine-phosphorylated p120 Cas, but not tyrosine-phosphorylated CTNNB1, now is detected in E-cadherin complexes.
The tyrosine-phosphorylated CTNNB1 also shows increased detergent solubility, suggesting a decreased association with the actin cytoskeleton.
decreased tyrosine phosphorylation of CTNNB1 is accompanied by increased interaction with both E-cadherin and the detergent insoluble cytoskeletal fraction
PMID:12051714
Activation of the canonical Wnt signalling pathway results in stabilisation and nuclear translocation of b-catenin.
In the absence of a Wnt signal, b-catenin is phosphorylated at four conserved serine and threonine residues at the N-terminus of the protein, which results in b-catenin ubiquitination and proteasome-dependent degradation.
The phosphorylation of 3 of these residues, Thr41, Ser37, and Ser33, is mediated by glycogen synthase kinase-3 (GSK-3) in a sequential manner, beginning from the C-terminal Thr41.
It has recently been shown that the GSK-3 dependent phosphorylation of b-catenin requiresprior priming through phosphorylation of Ser45
GSK-3b wasfound to be unable to phosphorylate b-catenin at Ser45 in vitro and in intact cells.
In vitro, CK1, but not CK2, phosphorylates Ser45. Ser45 phosphorylation in intact cells is not mediated by CK1e, a known positive regulator of Wnt signalling.
PMID:11955436
Wnt regulation of b-catenin degradation is essential for development and carcinogenesis.
b-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation.
This phosphorylation is believed to be performed by GSK3B in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC).
There is another Axin-associated kinase, whose phosphorylation of b-catenin precedes and is required for subsequent GSK-3 phosphorylation of b-catenin.
This priming kinase is casein kinase I -alpha (CSNK1A1).
PMID:11967263
Tyr-216 phosphorylation in GSK3B is required for GSK-mediated down-regulation of b-catenin activity.
PMID:8666229
Xenopus GSK3 functions to destabilize b-catenin and thus decrease the amount of b-catenin available for signaling


Modifications:
In compartment: Cytoplasm
  1. CHUK@Cytoplasm map

Participates in complexes:
In compartment: TNFRSF1 Receptor Complex

  1. CHUK:​IKBKG:​IKK_beta_*@TNFRSF1 Receptor Complex map

  2. CHUK:​IKBKG:​IKK_beta_*|​pho@TNFRSF1 Receptor Complex map

Participates in reactions:
As Reactant or Product:

  1. IKK_beta_*@Cytoplasm map + CHUK@Cytoplasm map + IKBKG@TNFRSF1 Receptor Complex map map CHUK:​IKBKG:​IKK_beta_*@TNFRSF1 Receptor Complex map

  2. CHUK:​IKBKG:​IKK_beta_*@TNFRSF1 Receptor Complex map map CHUK:​IKBKG:​IKK_beta_*|​pho@TNFRSF1 Receptor Complex map

As Catalyser:

  1. NFKBIA@Cytoplasm map map NFKBIA|​pho@Cytoplasm map

  2. APC|​pho:​AXIN1|​pho:​_beta_-Catenin*@Cytoplasm map map APC|​pho:​AXIN1|​pho:​_beta_-Catenin*|​pho@Cytoplasm map

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