PMID:24302570

Citation	Araki, K, Kawauchi, K, Hirata, H, Yamamoto, M and Taya, Y (2013) Cytoplasmic translocation of the retinoblastoma protein disrupts sarcomeric organization. Elife 2:e01228
Abstract	Skeletal muscle degeneration is a complication arising from a variety of chronic diseases including advanced cancer. Pro-inflammatory cytokine TNF-α plays a pivotal role in mediating cancer-related skeletal muscle degeneration. Here, we show a novel function for retinoblastoma protein (Rb), where Rb causes sarcomeric disorganization. In human skeletal muscle myotubes (HSMMs), up-regulation of cyclin-dependent kinase 4 (CDK4) and concomitant phosphorylation of Rb was induced by TNF-α treatment, resulting in the translocation of phosphorylated Rb to the cytoplasm. Moreover, induced expression of the nuclear exporting signal (NES)-fused form of Rb caused disruption of sarcomeric organization. We identified mammalian diaphanous-related formin 1 (mDia1), a potent actin nucleation factor, as a binding partner of cytoplasmic Rb and found that mDia1 helps maintain the structural integrity of the sarcomere. These results reveal a novel non-nuclear function for Rb and suggest a potential mechanism of TNF-α-induced disruption of sarcomeric organization. DOI: http://dx.doi.org/10.7554/eLife.01228.001.
Links	PubMed PMC3843810 Online version:10.7554/eLife.01228
Keywords
edit table

Significance

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:RBL1	Contributes to	GO:0006611: protein export from nucleus	ECO:0000314:		P		Figure 1:Phosphorylation of retinoblastoma proteins by up-regulation of cyclin-dependent kinase 4 triggers its cytoplasmic translocation from the nucleus in human skeletal muscle myotubes.	complete CACAO 9459

See Help:References for how to manage references in GONUTS.