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. Crown Copyright

Additional Metadata
Keywords Glia, Myosin, MYPT1, Neurons, Proteasomal pathway, SIAH2
Persistent URL dx.doi.org/10.1016/j.yexcr.2009.09.001
Journal Experimental Cell Research
Citation
Twomey, E. (Erin), Li, Y. (Yan), Lei, J. (Joy), Sodja, C. (Caroline), Ribecco-Lutkiewicz, M. (Maria), Smith, B. (Brandon), … Sikorska, M. (Marianna). (2010). Regulation of MYPT1 stability by the E3 ubiquitin ligase SIAH2. Experimental Cell Research, 316(1), 68–77. doi:10.1016/j.yexcr.2009.09.001