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

doi:10.1016/j.bbrc.2004.02.004

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 journal › Article › peer-review

49 Scopus citations

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 language	English (US)
Pages (from-to)	1070-1076
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	315
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2004.02.004
State	Published - Mar 19 2004
Externally published	Yes

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

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10.1016/j.bbrc.2004.02.004

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@article{b18d1a6ff52044e7a49a8026f43b6b45,

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, Retinoid X receptor, SKIP, Transcription, Vitamin D, p300",

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.}",

note = "Funding Information: We especially thank Drs. A. Kouzmenko, J. Segars, and R. Dahl for critical review of the manuscript; Jonine Figueroa, Sudip Datta, and Colette Fong and Nathan Doyle for technical assistance; and the following scientific colleagues for generously providing plasmids: M. Henderson, J. Segars, B. May, B. O{\textquoteright}Malley, L. Jameson, T. Tagami, P. Polly, T. Hienzel, and R. Eckner. G.M.L. was recipient of an Australian National Health and Medical Research Council Post-Graduate Medical Scholarship and a Royal Australasian College of Physicians and Vincent Fairfax Family Foundation Research Fellowship and L.L.I. a recipient of an Australian Postgraduate Award during this study. This work was supported in part by NIH Public service Grants CA28146 and CA42573 to M.J. Hayman and a NHMRC Centre grant to the Bone and Mineral Research Program and the Garvan Institute of Medical Research.",

year = "2004",

month = mar,

day = "19",

doi = "10.1016/j.bbrc.2004.02.004",

language = "English (US)",

volume = "315",

pages = "1070--1076",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "4",

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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.

N1 - Funding Information: We especially thank Drs. A. Kouzmenko, J. Segars, and R. Dahl for critical review of the manuscript; Jonine Figueroa, Sudip Datta, and Colette Fong and Nathan Doyle for technical assistance; and the following scientific colleagues for generously providing plasmids: M. Henderson, J. Segars, B. May, B. O’Malley, L. Jameson, T. Tagami, P. Polly, T. Hienzel, and R. Eckner. G.M.L. was recipient of an Australian National Health and Medical Research Council Post-Graduate Medical Scholarship and a Royal Australasian College of Physicians and Vincent Fairfax Family Foundation Research Fellowship and L.L.I. a recipient of an Australian Postgraduate Award during this study. This work was supported in part by NIH Public service Grants CA28146 and CA42573 to M.J. Hayman and a NHMRC Centre grant to the Bone and Mineral Research Program and the Garvan Institute of Medical Research.

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 - Retinoid X receptor

KW - SKIP

KW - Transcription

KW - Vitamin D

KW - p300

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U2 - 10.1016/j.bbrc.2004.02.004

DO - 10.1016/j.bbrc.2004.02.004

M3 - Article

C2 - 14985122

AN - SCOPUS:1342302833

SN - 0006-291X

VL - 315

SP - 1070

EP - 1076

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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