Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300

Gary M. Leong, Nanthakumar Subramaniam, Laura L. Issa, Janelle B. Barry, Tomoshige Kino, Paul H. Driggers, Michael J. Hayman, John A. Eisman, Edith M. Gardiner

Research output: Contribution to journalArticle

Abstract

Ski-interacting protein (SKIP), a vitamin D receptor (VDR) coactivator, also functions as a repressor in Notch signalling in association with the corepressor SMRT. Here we show that SKIP bifunctionally modulates (activates or represses) Retinoid-X receptor (RXR)- and VDR-dependent gene transcription in a cell line-specific manner, with activation in CV-1 and repression in P19 cells. The coactivator function of SKIP in these cells appeared to correlate with the relative level and ratio of expression of N-CoR and p300, with greater SKIP activation in higher p300-expressing and lower N-CoR-expressing cell-lines. C-terminal deletion of SKIP (Δ334-536aa) was associated with strong activation in both CV-1 and P19 cells. The corepressors N-CoR and SMRT and the coregulator p300 interacted with SKIP through the same N-terminal region (1-200aa). Overall these results suggest that transcriptional action of SKIP may depend on distinct functional domains and cell line-specific interactions with both corepressors and coactivators.

Original languageEnglish (US)
Pages (from-to)1070-1076
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume315
Issue number4
DOIs
StatePublished - Mar 19 2004

Keywords

  • N-CoR/SMRT
  • NcoA-62
  • Nuclear receptor
  • Retinoid X receptor
  • SKIP
  • Transcription
  • Vitamin D
  • p300

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300'. Together they form a unique fingerprint.

  • Cite this

    Leong, G. M., Subramaniam, N., Issa, L. L., Barry, J. B., Kino, T., Driggers, P. H., Hayman, M. J., Eisman, J. A., & Gardiner, E. M. (2004). Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300. Biochemical and Biophysical Research Communications, 315(4), 1070-1076. https://doi.org/10.1016/j.bbrc.2004.02.004