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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.

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Acknowledgements

We are particularly grateful to Dr Anita Roberts for help, assistance and encouragement to investigate SNIP1. We thank Maren Oehlmann for help with gel filtration analysis, Rosie Clarke for help with FACS analysis, all the members of the NDP laboratory and the Division of Gene Regulation and Expression at the University of Dundee for their help and assistance. NDP is funded by a Royal Society University Fellowship, KCR was formally a BBSRC PhD student but is now funded by the Association of International Cancer Research (AICR). TOH and NW are funded by a Wellcome Trust Senior Research Fellowship.

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Correspondence to Neil D Perkins.

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Roche, K., Wiechens, N., Owen-Hughes, T. et al. The FHA domain protein SNIP1 is a regulator of the cell cycle and cyclin D1 expression. Oncogene 23, 8185–8195 (2004). https://doi.org/10.1038/sj.onc.1208025

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Keywords

  • forkhead-associated domain
  • p300
  • AP-1
  • Swi/Snf
  • BRG1

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