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PMID:16115198

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Citation

Collart, C, Remacle, JE, Barabino, S, van Grunsven, LA, Nelles, L, Schellens, A, Van de Putte, T, Pype, S, Huylebroeck, D and Verschueren, K (2005) Smicl is a novel Smad interacting protein and cleavage and polyadenylation specificity factor associated protein. Genes Cells 10:897-906

Abstract

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.

Links

PubMed Online version:10.1111/j.1365-2443.2005.00887.x

Keywords

Activin Receptors, Type I/metabolism; Animals; Base Sequence; CHO Cells; COS Cells; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Cells, Cultured; Cercopithecus aethiops; Cleavage And Polyadenylation Specificity Factor/chemistry; Cleavage And Polyadenylation Specificity Factor/metabolism; Cloning, Molecular; Cricetinae; Humans; Mice; Models, Biological; Molecular Sequence Data; Nuclear Proteins/chemistry; Nuclear Proteins/metabolism; RNA Precursors/metabolism; Sequence Homology, Amino Acid; Signal Transduction; Time Factors; Transcription, Genetic; Transfection; Transforming Growth Factor beta/metabolism; Two-Hybrid System Techniques

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:CPSF2

part_of

GO:0005847: mRNA cleavage and polyadenylation specificity factor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMAD5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CHP0

F

Seeded From UniProt

complete

MOUSE:SMAD4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CHP0

F

Seeded From UniProt

complete

MOUSE:ACV1B

acts_upstream_of_or_within

GO:0032924: activin receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMAD2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q8CHP0

F

Seeded From UniProt

complete

MOUSE:ZC3H3

acts_upstream_of_or_within

GO:0032927: positive regulation of activin receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1338944

P

Seeded From UniProt

complete

MOUSE:ZC3H3

acts_upstream_of_or_within

GO:0031124: mRNA 3'-end processing

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ZC3H3

part_of

GO:0005847: mRNA cleavage and polyadenylation specificity factor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ZC3H3

enables

GO:0046332: SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P97471

F

Seeded From UniProt

complete

MOUSE:ZC3H3

enables

GO:0070412: R-SMAD binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ZC3H3

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CPSF3

part_of

GO:0005847: mRNA cleavage and polyadenylation specificity factor complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ZEB2

enables

GO:0070412: R-SMAD binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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