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.

doi:10.1016/j.bbrc.2004.02.004

Cited by 52 publications

(34 citation statements)

References 35 publications

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“…Subsequently, Skip has been reported to act both as a corepressor in association with the CSL corepressors SMRT/NCoR and Sharp and as an enhancer or coactivator of the Notch signaling pathway (13,19,29,39). The mechanistic details of how Skip works in Notch transcriptional activation are not known.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, during the transition from preactivation complex to activation complex, it is not difficult to envision how CSL can displace Skip by steric hindrance from the complex, since both interact with the ankyrin repeat of Notch (26,33,36,39). Depending on Notch presence or absence, it has been reported that Skip can be found forming part of a CSL-repressor complex or a transcriptional activation complex (13,19,29,39). The data that support the model in which Skip is associated with the Notch activation complex come from chromatin immunoprecipitation (ChIP) analysis, in which Skip and other proteins can be detected sitting on the chromatin when Notch is present (12).…”

Section: Discussionmentioning

confidence: 99%

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Assembly of a Notch Transcriptional Activation Complex Requires Multimerization

Carpió

Kaplan

Weaver

et al. 2011

Molecular and Cellular Biology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Assembly of a Notch Transcriptional Activation Complex Requires Multimerization

Carpió

Kaplan

Weaver

et al. 2011

Molecular and Cellular Biology

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“…This finding is reminiscent of the role of SKIP during Notch signaling. SKIP was identified as a component of a corepressor complex that represses RBPJ transcriptional activity, but it was subsequently shown to bind to the Notch intracellular domain and to promote Notch activation (28,51). It is possible that Rbm15 functions in a similar manner, associating with different cofactors in a cell-specific context that determines either an activation or a repression activity.…”

Section: Discussionmentioning

confidence: 99%

Rbm15 Modulates Notch-Induced Transcriptional Activation and Affects Myeloid Differentiation

Renda

Wang

et al. 2007

Molecular and Cellular Biology

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RBM15 is the fusion partner with MKL in the t(1;22) translocation of acute megakaryoblastic leukemia. To understand the role of the RBM15-MKL1 fusion protein in leukemia, we must understand the normal functions of RBM15 and MKL. Here, we show a role for Rbm15 in myelopoiesis. Rbm15 is expressed at highest levels in hematopoietic stem cells and at more moderate levels during myelopoiesis of murine cell lines and primary murine cells. Decreasing Rbm15 levels with RNA interference enhances differentiation of the 32DWT18 myeloid precursor cell line. Conversely, enforced expression of Rbm15 inhibits 32DWT18 differentiation. We show that Rbm15 alters Notch-induced HES1 promoter activity in a cell type-specific manner. Rbm15 inhibits Notch-induced HES1 transcription in nonhematopoietic cells but stimulates this activity in hematopoietic cell lines, including 32DWT18 and human erythroleukemia cells. Moreover, the N terminus of Rbm15 coimmunoprecipitates with RBPJ, a critical factor in Notch signaling, and the Rbm15 N terminus has a dominant negative effect, impairing activation of HES1 promoter activity by full-length-Rbm15. Thus, Rbm15 is differentially expressed during hematopoiesis and may act to inhibit myeloid differentiation in hematopoietic cells via a mechanism that is mediated by stimulation of Notch signaling via RBPJ.Acute megakaryoblastic leukemia (AML-M7, also referred to as AMKL) comprises approximately 10% of childhood AML, in which it frequently presents in infants with bone marrow fibrosis and progresses rapidly, with a median survival of 8 months. This phenotype is associated with the t(1;22)(p13; q13) translocation, which was first observed in several infants with AML-M7 (5) and subsequently confirmed by others to be associated almost exclusively with this type of AML (2, 30, 31, 34). The t(1;22) translocation has only very rarely been associated with the AML-M7 cases that occur in association with trisomy 21; in general, AML-M7 with trisomy 21 is nearly always associated with mutations in the GATA1 gene (14, 32). In t(1;22), the breakpoint on chromosome 1p13 is within a gene that has been variably named RBM15 for RNA-binding motif protein 15 and OTT (for one twenty-two translocation), and the breakpoint on chromosome 22 is within the MKL1 gene (also known as MAL or BSAC).The MKL1 gene product is a 4.5-kb transcript that is widely expressed in normal tissues (35) and encodes one of three members of the myocardin family. While these three members, i.e., MKL1, MKL2, and myocardin, are only 35% similar to one another at the protein level, they have several highly conserved domains, including RPEL repeats in the N terminus, a region with a B (basic amino acid) box and a glutamine-rich domain that is involved in binding to serum response factor, a leucine zipper-like domain that plays a role in homo-and heterodimerization, and a C-terminal transactivation domain. These proteins also have a SAP domain that, based on its homology to SAF-B, is predicted to associate with matrix attachment regions of transcrip...

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“…The Ski-interacting protein SKIP (Snw1 and NCoA62) is a required transcriptional coactivator for many newly induced genes (Leong et al 2001(Leong et al , 2004Zhang et al 2003;Folk et al 2004;MacDonald et al 2004) and counteracts transcriptional repression by retinoblastoma (Prathapam et al 2002). The SKIP homologs in Saccharomyces cerevisiae (Prp45) and Drosophila (BX42) are essential for cell viability, splicing Makarov et al 2002;Gahura et al 2009), and nuclear export of spliced mRNAs (Farny et al 2008).…”

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confidence: 99%

SKIP counteracts p53-mediated apoptosis via selective regulation of p21^Cip1 mRNA splicing

Chen¹,

Zhang²,

Jones³

2011

Genes Dev.

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The Ski-interacting protein SKIP/SNW1 functions as both a splicing factor and a transcriptional coactivator for induced genes. We showed previously that transcription elongation factors such as SKIP are dispensable in cells subjected to DNA damage stress. However, we report here that SKIP is critical for both basal and stress-induced expression of the cell cycle arrest factor p21Cip1 . RNAi chromatin immunoprecipitation (RNAi-ChIP) and RNA immunoprecipitation (RNA-IP) experiments indicate that SKIP is not required for transcription elongation of the gene under stress, but instead is critical for splicing and p21Cip1 protein expression. SKIP interacts with the 39 splice site recognition factor U2AF65 and recruits it to the p21 Cip1 gene and mRNA. Remarkably, SKIP is not required for splicing or loading of U2AF65 at other investigated p53-induced targets, including the proapoptotic gene PUMA. Consequently, depletion of SKIP induces a rapid down-regulation of p21Cip1 and predisposes cells to undergo p53-mediated apoptosis, which is greatly enhanced by chemotherapeutic DNA damage agents. ChIP experiments reveal that SKIP is recruited to the p21 Cip1 , and not PUMA, gene promoters, indicating that p21Cip1 gene-specific splicing is predominantly cotranscriptional. The SKIP-associated factors DHX8 and Prp19 are also selectively required for p21 Cip1 expression under stress. Together, these studies define a new step that controls cancer cell apoptosis.

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

Cited by 52 publications

References 35 publications

Assembly of a Notch Transcriptional Activation Complex Requires Multimerization

Assembly of a Notch Transcriptional Activation Complex Requires Multimerization

Rbm15 Modulates Notch-Induced Transcriptional Activation and Affects Myeloid Differentiation

SKIP counteracts p53-mediated apoptosis via selective regulation of p21^Cip1 mRNA splicing

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

Cited by 52 publications

References 35 publications

Assembly of a Notch Transcriptional Activation Complex Requires Multimerization

Assembly of a Notch Transcriptional Activation Complex Requires Multimerization

Rbm15 Modulates Notch-Induced Transcriptional Activation and Affects Myeloid Differentiation

SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing

Contact Info

Product

Resources

About

SKIP counteracts p53-mediated apoptosis via selective regulation of p21^Cip1 mRNA splicing