a(HBP:crebinostat) directlyDecreases act(p(HGNC:HDAC6))

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PubMed:25546293

The N-terminus of β-catenin has phosphorylation, ubiquitination, and acetylation sites that regulate its stability and signaling. In the absence of a Wnt signal, Ser33, Ser37, and Thr41 are constitutively phosphorylated by glycogen synthase kinase 3β (GSK3β). β-Catenin phosphorylated at these sites is recognized by β-transducin repeat-containing protein (βTrCP), which results in ubiquitination and degradation by the ubiquitin-proteasome pathway. The N-terminal regulatory domain of β-catenin also includes Ser45, a phosphorylation site for Casein Kinase 1α (CK1α) and Lys49, which is acetylated by the acetyltransferase p300/CBP-associated factor (PCAF). The relevance of Lys49 acetylation and Ser45 phosphorylation to the function of β-catenin is an active area of investigation. We find that HDAC6 inhibitors increase Lys49 acetylation and Ser45 phosphorylation but do not affect Ser33, Ser37, and Thr41 phosphorylation. Lys49 acetylation results in decreased ubiquitination of β-catenin in the presence of proteasome inhibition. While increased Lys49 acetylation does not affect total levels of β-catenin, it results in increased membrane localization of β-catenin.

Related Edges 15

• a(CHEBI:vorinostat) directlyDecreases act(p(HGNC:HDAC6))
• a(CHEBI:vorinostat) increases p(HGNC:CTNNB1, pmod(Ac, Lys, 49))
• a(HBP:crebinostat) increases p(HGNC:CTNNB1, pmod(Ac, Lys, 49))
• p(HGNC:CSNK1A1) increases p(HGNC:CTNNB1, pmod(Ph, Ser, 35))
• p(HGNC:CTNNB1, pmod(Ac, Lys, 49)) decreases p(HGNC:CTNNB1, pmod(Ub))
• p(HGNC:CTNNB1, pmod(Ac, Lys, 49)) increases p(HGNC:CTNNB1, loc(GO:membrane))
• p(HGNC:CTNNB1, pmod(Ac, Lys, 49)) negativeCorrelation act(p(HGNC:HDAC6))
• p(HGNC:CTNNB1, pmod(Ph, Ser, 33)) increases deg(p(HGNC:CTNNB1))
• p(HGNC:CTNNB1, pmod(Ph, Ser, 37)) increases deg(p(HGNC:CTNNB1))
• p(HGNC:CTNNB1, pmod(Ph, Thr, 41)) increases deg(p(HGNC:CTNNB1))
• act(p(HGNC:GSK3B), ma(kin)) directlyIncreases p(HGNC:CTNNB1, pmod(Ph, Ser, 33))
• act(p(HGNC:GSK3B), ma(kin)) directlyIncreases p(HGNC:CTNNB1, pmod(Ph, Ser, 37))
• act(p(HGNC:GSK3B), ma(kin)) directlyIncreases p(HGNC:CTNNB1, pmod(Ph, Thr, 41))
• act(p(HGNC:HDAC6)) negativeCorrelation p(HGNC:CTNNB1, pmod(Ac, Lys, 49))
• p(HGNC:KAT2B) increases p(HGNC:CTNNB1, pmod(Ac, Lys, 49))

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.

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