title: Actin-cytoskeleton polymerization differentially controls the stability of Ski and SnoN co-repressors in normal but not in transformed hepatocytes.
abstract: BACKGROUND
  Ski and SnoN proteins function as transcriptional co-repressors in the TGF-β pathway. They regulate cell proliferation and differentiation, and their aberrant expression results in altered TGF-β signalling, malignant transformation, and alterations in cell proliferation.
  
  
  METHODS
  We carried out a comparative characterization of the endogenous Ski and SnoN protein regulation by TGF-β, cell adhesion disruption and actin-cytoskeleton rearrangements between normal and transformed hepatocytes; we also analyzed Ski and SnoN protein stability, subcellular localization, and how their protein levels impact the TGF-β/Smad-driven gene transcription.
  
  
  RESULTS
  Ski and SnoN protein levels are lower in normal hepatocytes than in hepatoma cells. They exhibit a very short half-life and a nuclear/cytoplasmic distribution in normal hepatocytes opposed to a high stability and restricted nuclear localization in hepatoma cells. Interestingly, while normal cells exhibit a transient TGF-β-induced gene expression, the hepatoma cells are characterized by a strong and sustained TGF-β-induced gene expression. A novel finding is that Ski and SnoN stability is differentially regulated by cell adhesion and cytoskeleton rearrangements in the normal hepatocytes. The inhibition of protein turnover down-regulated both Ski and SnoN co-repressors impacting the kinetic of expression of TGF-β-target genes.
  
  
  CONCLUSIONS
  Normal regulatory mechanisms controlling Ski and SnoN stability, subcellular localization and expression are altered in hepatocarcinoma cells.
  
  
  CONCLUSIONS
  This work provides evidence that Ski and SnoN protein regulation is far more complex in normal than in transformed cells, since many of the normal regulatory mechanisms are lost in transformed cells.
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. México D.F., 04510, México.
authors.forename: Cassandre
authors.initials: C
authors.lastname: Caligaris
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. México D.F., 04510, México.
authors.forename: Genaro
authors.initials: G
authors.lastname: Vázquez-Victorio
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. México D.F., 04510, México.
authors.forename: Marcela
authors.initials: M
authors.lastname: Sosa-Garrocho
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. México D.F., 04510, México.
authors.forename: Diana G
authors.initials: DG
authors.lastname: Ríos-López
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, México D.F., 14080, México.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Marín-Hernández
authors.affiliation: Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. México D.F., 04510, México. Electronic address: mmacias@ifc.unam.mx.
authors.forename: Marina
authors.initials: M
authors.lastname: Macías-Silva
mesh_terms: D000199:Actins / Q000737:chemistry*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D058105:Polymerization; D055550:Protein Stability; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D051785:Smad Proteins / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; C060615:SKIL protein, human; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C060614:SKI protein, human
keywords: Hepatocarcinoma; Protein stability; Ski; SnoN; TGF-β; Transcriptional regulation