Regulation of MYPT1 stability by the E3 ubiquitin ligase SIAH2

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DOIResolve DOI: http://doi.org/10.1016/j.yexcr.2009.09.001
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TypeArticle
Journal titleExperimental Cell Research
Volume316
Issue1
Pages6877; # of pages: 10
SubjectSIAH2; MYPT1; Proteasomal pathway; Myosin; Neurons; Glia
AbstractMyosin phosphatase target subunit 1 (MYPT1), together with catalytic subunit of type1 δ isoform (PP1cδ) and a small 20-kDa regulatory unit (M20), form a heterotrimeric holoenzyme, myosin phosphatase (MP), which is responsible for regulating the extent of myosin light chain phosphorylation. Here we report the identification and characterization of a molecular interaction between Seven in absentia homolog 2 (SIAH2) and MYPT1 that resulted in the proteasomal degradation of the latter in mammalian cells, including neurons and glia. The interaction involved the substrate binding domain of SIAH2 (aa 116–324) and a central region of MYPT1 (aa 445–632) containing a degenerate consensus Siah-binding motif RLAYVAP (aa 493–499) evolutionally conserved from fish to humans. These findings suggest a novel mechanism whereby the ability of MP to modulate myosin light chain might be regulated by the degradation of its targeting subunit MYPT1 through the SIAH2-ubiquitin-proteasomal pathway. In this manner, the turnover of MYPT1 would serve to limit the duration and/or magnitude of MP activity required to achieve a desired physiological effect.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences
Peer reviewedYes
NPARC number15462306
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Record identifier3a2b2a1d-ac16-4386-85e6-59e0023ecb9f
Record created2010-08-16
Record modified2016-05-09
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