| DOI | Resolve DOI: https://doi.org/10.1016/j.yexcr.2009.09.001 |
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| Author | Search for: Twomey, Erin1; Search for: Li, Yan1; Search for: Lei, Joy1; Search for: Sodja, Caroline1; Search for: Ribecco-Lutkiewicz, Maria1; Search for: Smith, Brandon1; Search for: Fang, Hung1; Search for: Bani-Yaghoub, Mahmud1; Search for: McKinnell, Iain1; Search for: Sikorska, Marianna1 |
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| Affiliation | - National Research Council of Canada. NRC Institute for Biological Sciences
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| Format | Text, Article |
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| Subject | SIAH2; MYPT1; Proteasomal pathway; Myosin; Neurons; Glia |
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| Abstract | Myosin 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. |
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| Publication date | 2010-01-01 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 15462306 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 3a2b2a1d-ac16-4386-85e6-59e0023ecb9f |
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| Record created | 2010-08-16 |
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| Record modified | 2020-04-17 |
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