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
Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Biochem Biophys Res Commun. 2004 Mar 19;315(4):1070-6. doi: 10.1016/j.bbrc.2004.02.004.
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 (delta334-536 aa) 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 (1-200 aa). 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.
Ski相互作用蛋白（SKIP）是一种维生素D受体（VDR）共激活因子，它还与共抑制因子SMRT结合，在Notch信号通路中发挥抑制作用。我们在此表明，SKIP以细胞系特异性方式对视黄酸X受体（RXR）和VDR依赖的基因转录进行双功能调节（激活或抑制），在CV-1细胞中起激活作用，而在P19细胞中起抑制作用。SKIP在这些细胞中的共激活功能似乎与N-CoR和p300的相对表达水平及比例相关，在p300表达较高且N-CoR表达较低的细胞系中，SKIP的激活作用更强。SKIP的C端缺失（第334 - 536位氨基酸缺失）与CV-1和P19细胞中的强激活作用相关。共抑制因子N-CoR和SMRT以及共调节因子p300通过相同的N端区域（第1 - 200位氨基酸）与SKIP相互作用。总体而言，这些结果表明SKIP的转录作用可能取决于不同的功能结构域以及与共抑制因子和共激活因子的细胞系特异性相互作用。
