Novel Regulation of Ski Protein Stability and Endosomal Sorting by Actin Cytoskeleton Dynamics in Hepatocytes

作者：Vazquez Victorio Genaro; Caligaris Cassandre; Del Valle Espinosa Eugenio; Sosa Garrocho Marcela; Gonzalez Arenas Nelly R; Reyes Cruz Guadalupe; Briones Orta Marco A; Macias Silva Marina^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290(7): 4487-4499.

DOI：10.1074/jbc.M114.579532

TGF-beta-induced antimitotic signals are highly regulated during cell proliferation under normal and pathological conditions, such as liver regeneration and cancer. Up-regulation of the transcriptional cofactors Ski and SnoN during liver regeneration may favor hepatocyte proliferation by inhibiting TGF-beta signals. In this study, we found a novel mechanism that regulates Ski protein stability through TGF-beta and G protein-coupled receptor (GPCR) signaling. Ski protein is distributed between the nucleus and cytoplasm of normal hepatocytes, and the molecular mechanisms controlling Ski protein stability involve the participation of actin cytoskeleton dynamics. Cytoplasmic Ski is partially associated with actin and localized in cholesterol-rich vesicles. Ski protein stability is decreased by TGF-beta/Smads, GPCR/Rho signals, and actin polymerization, whereas GPCR/cAMP signals and actin depolymerization promote Ski protein stability. In conclusion, TGF-beta and GPCR signals differentially regulate Ski protein stability and sorting in hepatocytes, and this cross-talk may occur during liver regeneration.

• 出版日期2015-2-13