title: Proteasomal degradation of retinoblastoma-related p130 during adipocyte differentiation.
abstract: Within 24 h of hormonally stimulated 3T3-L1 adipocyte differentiation, there are dramatic changes in the protein levels of p130 and p107, two members of the retinoblastoma tumor suppressor gene family. Designated the "p103:p107" switch, this alteration is characterized by a rapid and transient drop in p130 protein levels accompanied by a transient increase in both p107 mRNA and protein levels. Using protease inhibitors, the specific proteolytic pathway involved in degradation of p130 was examined. Treatment of cells with N-acetyl-leu-leu-norleucinal, an inhibitor that blocks proteolytic activity of type I calpain and the 26S proteasome, resulted in a complete block in the degradation of p130 protein, as well as adipocyte differentiation, suggesting that one of these pathways is involved in regulating p130 protein levels. Similar analysis with lactacystin, a specific inhibitor of the 26S proteasome, also resulted in a complete block in both differentiation and p130 degradation. Furthermore, both inhibitors blocked the increase in p107 protein levels normally observed on Day 1, suggesting that the p130:p107 switch is required for adipocyte differentiation and one of the early molecular events involved in activating the p130:p107 switch is the specific degradation of p130 by the 26S proteasome.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Arkansas 72205, USA.
authors.forename: Audra M
authors.initials: AM
authors.lastname: Prince
authors.forename: Julie S
authors.initials: JS
authors.lastname: May
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Burton
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lyle
authors.forename: Robert E
authors.initials: RE
authors.lastname: McGehee
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D050717:Retinoblastoma-Like Protein p130; C063261:acetylleucyl-leucyl-norleucinal; C067713:lactacystin; D010447:Peptide Hydrolases; D002154:Calpain; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000111:Acetylcysteine