Smicl is a novel Smad interacting protein and cleavage and polyadenylation specificity factor associated protein.
Ligand-bound receptors of the Transforming Growth Factor-beta (TGF-beta) family promote the formation of complexes between Smad proteins that subsequently accumulate in the nucleus and interact there with other transcriptional regulators, leading to modulation of target gene expression. We identified a novel nuclear protein, Smicl, which binds to Smad proteins. Smicl and Smads cooperate and enhance TGF-beta mediated activation of a Smad-responsive reporter gene. A domain with five CCCH-type zinc fingers in Smicl is structurally and functionally, at least in vitro, similar to a domain in CPSF-30, the 30 kDa subunit of Cleavage and Polyadenylation Specificity Factor (CPSF). Like CPSF-30, Smicl can associate with some other CPSF subunits characterized previously. Its effect on the induction of a reporter gene for TGF-beta requires the cleavage/polyadenylation signal downstream of the coding sequence of that gene. Thus, Smicl is a novel protein that displays CPSF-30-like activities, interacts in the nucleus with activated Smads, and potentiates in TGF-beta stimulated cells Smad-dependent transcriptional responses, possibly in conjunction with the activity of CPSF complexes.
Collart
Clara
C
Department of Developmental Biology, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, B-3000 Leuven, Belgium.
Remacle
Jacques E
JE
Barabino
Silvia
S
van Grunsven
Leo A
LA
Nelles
Luc
L
Schellens
Ann
A
Van de Putte
Tom
T
Pype
Stefan
S
Huylebroeck
Danny
D
Verschueren
Kristin
K
D030201:Activin Receptors, Type I / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D039223:Cleavage And Polyadenylation Specificity Factor / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D039223:Cleavage And Polyadenylation Specificity Factor; D009687:Nuclear Proteins; D012322:RNA Precursors; C510764:Smicl protein, mouse; D016212:Transforming Growth Factor beta; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I