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

46 Citations (Scopus)

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
Pages (from-to)1070-1076
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume315
Issue number4
DOIs
Publication statusPublished - 19 Mar 2004
Externally publishedYes

Fingerprint

Cytoplasmic and Nuclear Receptors
Co-Repressor Proteins
Proteins
Calcitriol Receptors
Chemical activation
Cell Line
Retinoid X Receptors
Cells
Transcription
Genes
Association reactions

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300. / Leong, Gary M.; Subramaniam, Nanthakumar; Issa, Laura L.; Barry, Janelle B.; Kino, Tomoshige; Driggers, Paul H.; Hayman, Michael J.; Eisman, John A.; Gardiner, Edith M.

In: Biochemical and Biophysical Research Communications, Vol. 315, No. 4, 19.03.2004, p. 1070-1076.

Research output: Contribution to journalArticle

Leong, GM, Subramaniam, N, Issa, LL, Barry, JB, Kino, T, Driggers, PH, Hayman, MJ, Eisman, JA & Gardiner, EM 2004, 'Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300', Biochemical and Biophysical Research Communications, vol. 315, no. 4, pp. 1070-1076. https://doi.org/10.1016/j.bbrc.2004.02.004
Leong, Gary M. ; Subramaniam, Nanthakumar ; Issa, Laura L. ; Barry, Janelle B. ; Kino, Tomoshige ; Driggers, Paul H. ; Hayman, Michael J. ; Eisman, John A. ; Gardiner, Edith M. / Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 315, No. 4. pp. 1070-1076.
@article{7dde178d11f245b5bcf7e885645bc95b,
title = "Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300",
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.",
keywords = "N-CoR/SMRT, NcoA-62, Nuclear receptor, p300, Retinoid X receptor, SKIP, Transcription, Vitamin D",
author = "Leong, {Gary M.} and Nanthakumar Subramaniam and Issa, {Laura L.} and Barry, {Janelle B.} and Tomoshige Kino and Driggers, {Paul H.} and Hayman, {Michael J.} and Eisman, {John A.} and Gardiner, {Edith M.}",
year = "2004",
month = "3",
day = "19",
doi = "10.1016/j.bbrc.2004.02.004",
language = "English",
volume = "315",
pages = "1070--1076",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300

AU - Leong, Gary M.

AU - Subramaniam, Nanthakumar

AU - Issa, Laura L.

AU - Barry, Janelle B.

AU - Kino, Tomoshige

AU - Driggers, Paul H.

AU - Hayman, Michael J.

AU - Eisman, John A.

AU - Gardiner, Edith M.

PY - 2004/3/19

Y1 - 2004/3/19

N2 - 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.

AB - 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.

KW - N-CoR/SMRT

KW - NcoA-62

KW - Nuclear receptor

KW - p300

KW - Retinoid X receptor

KW - SKIP

KW - Transcription

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=1342302833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1342302833&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2004.02.004

DO - 10.1016/j.bbrc.2004.02.004

M3 - Article

C2 - 14985122

AN - SCOPUS:1342302833

VL - 315

SP - 1070

EP - 1076

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -