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 |
|---|---|
| Pages (from-to) | 1070-1076 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 315 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 19 Mar 2004 |
| Externally published | Yes |
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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 journal › Article
}
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 -