PCTA: a new player in TGF-beta signaling.
Transforming growth factor beta (TGF-beta) regulates a wide variety of biological activities by binding to cell surface serine/threonine kinase receptors. Canonical TGF-beta signaling is mediated by Smad proteins, which transduce the TGF-beta signal from the cell surface into the nucleus to regulate transcription. Upon TGF-beta binding and receptor activation, the TGF-beta receptor phosphorylates Smad2 and Smad3. SARA (Smad anchor for receptor activation) and cPML (cytoplasmic promyelocytic leukemia protein) recruit Smad2 and Smad3 for phosphorylation by the TGF-beta receptor. cPML is sequestered in the nucleus by the homeodomain protein TGIF (TG-interacting factor), a negative regulator of TGF-beta signaling. Recently, PCTA (PML competitor for TGIF association) has been shown to compete with cPML for binding to TGIF, resulting in the accumulation of cPML in the cytoplasm, where it mediates the interaction between Smad2/3 and SARA and coordinates the phosphorylation of Smad2 and Smad3 by the TGF-beta receptor. Accordingly, PCTA promotes TGF-beta-mediated transcriptional regulation and growth inhibition. Thus, PCTA defines a new regulator in TGF-beta signaling.
Liu
Fang
F
Center for Advanced Biotechnology and Medicine, Rutgers, The State University of New Jersey, 679 Hoes Lane, Piscataway, NJ 08854, USA. fangliu@cabm.rutgers.edu
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012097:Repressor Proteins; D051785:Smad Proteins; C097504:TGIF1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C475081:IRF2BP1 protein, human; D044767:Ubiquitin-Protein Ligases