SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

Short, Stephen; Malartre, Marianne; Sharpe, Colin

doi:10.1016/j.bbrc.2005.06.175

Cited by 22 publications

(52 citation statements)

References 38 publications

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“…This would in turn determine, in whole or in part, the position of the dimerization equilibrium (the proportion of Pcyt2 dimers as a/a, a/b, and b/b). Results from our multiple tissue mRNA expression study indicated that the relative levels of mPcyt2a and Pcyt2b transcripts do indeed vary from one tissue to another, as is often the case with alternatively spliced mRNAs (28).…”

Section: Discussionmentioning

confidence: 54%

Alternative splicing of CTP:phosphoethanolamine cytidylyltransferase produces two isoforms that differ in catalytic properties

Tie

Bakovic

2007

Journal of Lipid Research

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CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) catalyzes the rate-controlling reaction of the CDPethanolamine (Kennedy) pathway. We have previously established that Pcyt2 is encoded by a single gene that can be alternatively spliced from an internal exon into two transcripts, designated Pcyt2a and Pcyt2b. Little is currently known about the regulation of Pcyt2. Here, we functionally express both murine Pcyt2 (mPcyt2) transcripts and investigate the roles of the two proteins in the regulation of mPcyt2 activity. We demonstrate that the tagged and purified a and b proteins differ significantly in their kinetic properties. The K m of mPcyt2a for phosphoethanolamine was 318.4 mM, compared with 140.3 mM for mPcyt2b. The maximal velocities of the a and b isoforms at saturating conditions for both substrates were 138.0 and 114.4 nmol/ min/mmol enzyme, respectively. When phosphoethanolamine was used at a fixed concentration of 1 mM, the K m of mPcyt2a for CTP was 102.0 mM and that of mPcyt2b was 84.09 mM. Using a combination of nondenaturing PAGE, gel filtration chromatography, and immunoprecipitation, we provide evidence that mPcyt2a and mPcyt2b proteins can form both homodimeric and heterodimeric complexes. We show that alternative splicing of the mPcyt2 transcript is ubiquitous but could also be regulated in a tissue-specific manner, producing a variable ratio of mPcyt2a/mPcyt2b mRNAs. The expression of two distinct protein isoforms maybe an important mechanism by which Pcyt2 activity is regulated.-Tie, A., and M. Bakovic. Alternative splicing of CTP:phosphoethanolamine cytidylyltransferase produces two isoforms that differ in catalytic properties. J. Lipid Res. 2007Res. . 48: 2172Res. -2181

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Section: Discussionmentioning

confidence: 54%

Alternative splicing of CTP:phosphoethanolamine cytidylyltransferase produces two isoforms that differ in catalytic properties

Tie

Bakovic

2007

Journal of Lipid Research

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“…The mRNA transcripts from both the SMRT and the NCoR loci are subject to alternative splicing (18,(63)(64)(65)(66)(67)(68)(69)(70); the NCoR and SMRT splice variants that are the focus of this study are indicated in Fig. 1.…”

Section: The Relative Abundance Of the Different Corepressor Splice Vmentioning

confidence: 99%

“…We and others have reported that both SMRT and NCoR are expressed by alternative mRNA splicing to generate a diverse series of corepressor protein variants (18,(63)(64)(65)(66)(67)(68)(69)(70)(71). These splicevariants differ in the number and sequence of their RID domains, in the presence or absence of interaction surfaces for additional components of the corepressor holocomplex, in their affinity for different nuclear receptor partners, and in their response to protein kinase signals operating in cells (18,(63)(64)(65)(66)(67)(68)(69)(70)(71).…”

mentioning

confidence: 99%

“…These splicevariants differ in the number and sequence of their RID domains, in the presence or absence of interaction surfaces for additional components of the corepressor holocomplex, in their affinity for different nuclear receptor partners, and in their response to protein kinase signals operating in cells (18,(63)(64)(65)(66)(67)(68)(69)(70)(71). To better understand the impact of these alternative splicing events in a biologically relevant context, we turned to a study of adipocyte differentiation.…”

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confidence: 99%

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Alternative mRNA Splicing of Corepressors Generates Variants That Play Opposing Roles in Adipocyte Differentiation

Goodson

Mengeling

Jonas

et al. 2011

Journal of Biological Chemistry

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Background:The SMRT and NCoR corepressors play key biological roles in transcriptional repression. Results: Alternative mRNA splicing produces corepressor variants that can exert opposite effects on adipocyte differentiation. Conclusion: Corepressors are diversified by alternative mRNA splicing, allowing one locus to encode multiple proteins with distinct functions. Significance: Changes in alternative splicing may help drive the differentiation and customize the physiology of specific cell types.

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“…Extensive analysis has disclosed the presence in both molecules of 3 RIDs that can be expressed alternatively in a tissue-specific manner (18)(19)(20)(21). Despite their similarity the RIDs do not function equivalently.…”

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confidence: 99%

The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo

Astapova

Lee

Morales

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

140

134

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The thyroid hormone receptor (TR) has been proposed to regulate expression of target genes in the absence of triiodothyronine (T3) through the recruitment of the corepressors, NCoR and SMRT. Thus, NCoR and SMRT may play an essential role in thyroid hormone action, although this has never been tested in vivo. To accomplish this, we developed mice that express in the liver a mutant NCoR protein (L-NCoR⌬ID) that cannot interact with the TR. L-NCoR⌬ID mice appear grossly normal, however, when made hypothyroid the repression of many positively regulated T 3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by TR in the absence of T 3. Remarkably, in the euthyroid state, expression of many T 3-targets is also up-regulated in L-NCoR⌬ID mice, demonstrating that NCoR also determines the magnitude of the response to T 3 in euthyroid animals. Although positive T 3 targets were up-regulated in L-NCoR⌬ID mice in the hypo-and euthyroid state, there was little effect seen on negatively regulated T 3 target genes. Thus, NCoR is a specific regulator of T 3-action in vivo and mediates repression by the unliganded TR in hypothyroidism. Furthermore, NCoR appears to play a key role in determining the tissue-specific responses to similar levels of circulating T 3. Interestingly, NCoR recruitment to LXR is also impaired in this model, leading to activation of LXRtarget genes, further demonstrating that NCoR recruitment regulates multiple nuclear receptor signaling pathways.gene expression ͉ thyroid hormone receptor

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SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box

Cited by 22 publications

References 38 publications

Alternative splicing of CTP:phosphoethanolamine cytidylyltransferase produces two isoforms that differ in catalytic properties

Alternative splicing of CTP:phosphoethanolamine cytidylyltransferase produces two isoforms that differ in catalytic properties

Alternative mRNA Splicing of Corepressors Generates Variants That Play Opposing Roles in Adipocyte Differentiation

The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo

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