title: Transcriptional and post-translational regulation of the quiescence factor and putative tumor suppressor p150(Sal2).
abstract: The evolutionarily conserved SALL genes encode transcription factors with roles in embryonic development. The product of the SALL2 gene was first identified as a binding partner of the mouse polyoma virus large T antigen and later shown to possess tumor suppressor-like functions. Independent studies identified SALL2 as a factor regulating the quiescent state in human fibroblasts. Here, we investigate factors that regulate the expression of SALL2 and turnover of p150(Sal2) in growing vs. resting cells. The transcription factor AP4 increases along with SALL2 in quiescent cells and positively regulates SALL2 expression. TGFβ effectively inhibits expression of SALL2 and its regulator AP4 when added to quiescent fibroblasts. TGFβ repression of SALL2 and AP4 is independent of the induction of connective tissue growth factor (CTGF) by TGFβ. p150(Sal2) disappears rapidly on restoration of serum. In both growing fibroblasts and established ovarian surface epithelial cells, p150(Sal2) undergoes polyubiquitination and proteosomal degradation. A CUL4/DDB1 E3 ligase containing RBBP7 as the p150(Sal2) receptor has been identified as mediating the destruction of p150(Sal2) as cells transition from a quiescent to an actively growing state.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Chang K
authors.initials: CK
authors.lastname: Sung
authors.forename: Jean
authors.initials: J
authors.lastname: Dahl
authors.forename: Hyungshin
authors.initials: H
authors.lastname: Yim
authors.forename: Scott
authors.initials: S
authors.lastname: Rodig
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Benjamin
mesh_terms: D055513:Connective Tissue Growth Factor / Q000502:physiology; D044842:Cullin Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D052816:Foreskin / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D044967:Serum; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C526317:CCN2 protein, human; C517832:CUL4B protein, human; D044842:Cullin Proteins; C091435:DDB1 protein, human; D004268:DNA-Binding Proteins; D007976:Leupeptins; D009687:Nuclear Proteins; C470552:RBBP5 protein, human; C104147:SALL2 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C055473:enhancer-binding protein AP-4; D055513:Connective Tissue Growth Factor; D044767:Ubiquitin-Protein Ligases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde