title: Novel regulation of Ski protein stability and endosomal sorting by actin cytoskeleton dynamics in hepatocytes.
abstract: TGF-β-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-β signals. In this study, we found a novel mechanism that regulates Ski protein stability through TGF-β 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-β/Smads, GPCR/Rho signals, and actin polymerization, whereas GPCR/cAMP signals and actin depolymerization promote Ski protein stability. In conclusion, TGF-β and GPCR signals differentially regulate Ski protein stability and sorting in hepatocytes, and this cross-talk may occur during liver regeneration.
authors.affiliation: From the Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D. F. 04510, México and.
authors.forename: Genaro
authors.initials: G
authors.lastname: Vázquez-Victorio
authors.affiliation: From the Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D. F. 04510, México and.
authors.forename: Cassandre
authors.initials: C
authors.lastname: Caligaris
authors.affiliation: From the Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D. F. 04510, México and.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Del Valle-Espinosa
authors.affiliation: From the Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D. F. 04510, México and.
authors.forename: Marcela
authors.initials: M
authors.lastname: Sosa-Garrocho
authors.affiliation: From the Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D. F. 04510, México and.
authors.forename: Nelly R
authors.initials: NR
authors.lastname: González-Arenas
authors.affiliation: the Departamento de Biología Celular, CINVESTAV-IPN, México, D. F. 07000, México.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Reyes-Cruz
authors.affiliation: From the Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D. F. 04510, México and.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Briones-Orta
authors.affiliation: From the Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D. F. 04510, México and mmacias@ifc.unam.mx.
authors.forename: Marina
authors.initials: M
authors.lastname: Macías-Silva
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008115:Liver Regeneration; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C060614:SKI protein, human
keywords: Actin; Cytoskeleton; G Protein-coupled Receptor (GPCR); Proteasome; SMAD Transcription Factor; TGF-β; Transcription Corepressor