title: The FHA domain protein SNIP1 is a regulator of the cell cycle and cyclin D1 expression.
abstract: Smad nuclear interacting protein 1 (SNIP1) is an evolutionarily conserved protein containing a forkhead-associated (FHA) domain that regulates gene expression through interactions with multiple transcriptional regulators. Here, we have used short interfering RNAs (siRNAs) to knockdown SNIP1 expression in human cell lines. Surprisingly, we found that reduction in SNIP1 levels resulted in significantly reduced cell proliferation and accumulation of cells in the G1 phase of the cell cycle. Consistent with this result, we observed that cyclin D1 protein and mRNA levels were reduced. Moreover, SNIP1 depletion results in inhibition of cyclin D1 promoter activity in a manner dependent upon a previously characterized binding site for the AP-1 transcription factor family. SNIP1 itself is induced upon serum stimulation immediately prior to cyclin D1 expression. These effects were independent of the tumour suppressors p53 and retinoblastoma (Rb), but were consistent with an interaction with BRG1, a component of the ATP-dependent chromatin remodelling complex, Swi/Snf. These results define both a new function for SNIP1 and identify a previously unrecognized regulator of the cell cycle and cyclin D1 expression.
authors.affiliation: Division of Gene Regulation and Expression, School of Life Sciences, MSI/WTB Complex, Dow Street, University of Dundee, Dundee, DD1 5EH, UK.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Roche
authors.forename: Nicola
authors.initials: N
authors.lastname: Wiechens
authors.forename: Tom
authors.initials: T
authors.lastname: Owen-Hughes
authors.forename: Neil D
authors.initials: ND
authors.lastname: Perkins
mesh_terms: D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C411545:SNIP1 protein, human; D015534:Trans-Activators; D019938:Cyclin D1