The N-CoR-HDAC3 Nuclear Receptor Corepressor Complex Inhibits the JNK Pathway through the Integral Subunit GPS2

Zhang, Jinsong; Kalkum, Markus; Chait, Brian T.; Roeder, Robert G.

doi:10.1016/s1097-2765(02)00468-9

Cited by 377 publications

(421 citation statements)

References 32 publications

Supporting

Mentioning

400

Contrasting

Unclassified

Order By: Relevance

“…Biochemical purifications of both N-CoR/SMRT as well as HDAC3-associated proteins, mostly based on immunoaffinity precipitation followed by mass spectrometry, converged to this conclusion Wen et al, 2000;Li et al, 2000;Zhang et al, 2002;Yoon et al, 2003). At least in HeLa cells, the majority of cellular HDAC3 is found to associate with SMRT and N-CoR complexes.…”

Section: Hdac3 Complexesmentioning

confidence: 94%

“…Both TBL1 and TBLR1 interact directly with SMRT and N-CoR but not with HDAC3 Zhang et al, 2002;Yoon et al, 2003). In contrast to SMRT and N-CoR, TBL1 and TBLR1 are not required for HDAC3 enzymatic activity Zhang et al, 2002).…”

Section: Hdac3 Complexesmentioning

confidence: 99%

“…The purified N-CoR/SMRT complexes contain additional components including transducin b-like 1 (TBL1) Li et al, 2000), the TBL1-related protein (TBLR1) (Zhang et al, 2002;Yoon et al, 2003), and G protein pathway suppressor 2 (GPS-2) (Zhang et al, 2002;Yoon et al, 2003). Both TBL1 and TBLR1 interact directly with SMRT and N-CoR but not with HDAC3 Zhang et al, 2002;Yoon et al, 2003).…”

Section: Hdac3 Complexesmentioning

confidence: 99%

See 2 more Smart Citations

HDAC3: taking the SMRT-N-CoRrect road to repression

2007

View full text Add to dashboard Cite

Known histone deacetylases (HDACs) are divided into different classes, and HDAC3 belongs to Class I. Through forming multiprotein complexes with the corepressors SMRT and N-CoR, HDAC3 regulates the transcription of a plethora of genes. A growing list of nonhistone substrates extends the role of HDAC3 beyond transcriptional repression. Here, we review data on the composition, regulation and mechanism of action of the SMRT/ N-CoR-HDAC3 complexes and provide several examples of nontranscriptional functions, to illustrate the wide variety of physiological processes affected by this deacetylase. Furthermore, we discuss the implication of HDAC3 in cancer, focusing on leukemia. We conclude with some thoughts about the potential therapeutic efficacies of HDAC3 activity modulation.

show abstract

Section: Hdac3 Complexesmentioning

confidence: 94%

Section: Hdac3 Complexesmentioning

confidence: 99%

Section: Hdac3 Complexesmentioning

confidence: 99%

See 1 more Smart Citation

HDAC3: taking the SMRT-N-CoRrect road to repression

2007

View full text Add to dashboard Cite

show abstract

“…[51]). In addition, both SMRT and N-CoR participate in the formation of a stable multiprotein complex consisting of HDAC3, transducin (b)-like 1 (TBL1) [52,53] and GPS2, a protein involved in intracellular signaling [54]. A recent proteomic analysis of the components of the S. cerevisiae SET3 complex showed the presence of two HDACs, Hos2 and Hst1 [55].…”

Section: Dynamic Subcellular Localizationmentioning

confidence: 99%

Class II histone deacetylases: versatile regulators

2003

View full text Add to dashboard Cite

Histone acetylation and deacetylation play essential roles in modifying chromatin structure and regulating gene expression in eukaryotes. Histone deacetylases (HDACs) catalyze the deacetylation of lysine residues in the histone N-terminal tails and are found in large multiprotein complexes with transcriptional co-repressors. Human HDACs are grouped into three classes based on their similarity to known yeast factors: class I HDACs are similar to the yeast transcriptional repressor yRPD3, class II HDACs to yHDA1 and class III HDACs to ySIR2. In this review, we focus on the biology of class II HDACs. These newly discovered enzymes have been implicated as global regulators of gene expression during cell differentiation and development. We discuss their emerging biological functions and the molecular mechanisms by which they are regulated.

show abstract

“…When this fragmentation is induced on the slow time scale of resonant excitation within an ion trap mass spectrometer, the dissociation of singly-charged ions becomes especially selective, occurring largely adjacent to any aspartyl, glutamyl, or prolyl residues that may be present in the peptide [54,56]. Although the resulting low complexity spectra have proven to be of considerable utility for database-driven protein identification [57][58][59][60], we have generally considered these spectra to contain insufficient information to be useful for extensive de novo sequence determination.…”

mentioning

confidence: 99%

“De novo” peptide sequencing by MALDI-quadrupole-ion trap mass spectrometry: A preliminary study

Zhang

Krutchinsky

Chait

2003

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Collision-induced dissociation of singly charged peptide ions produced by resonant excitation in a matrix-assisted laser desorption/ionization (MALDI) ion trap mass spectrometer yields relatively low complexity MS/MS spectra that exhibit highly preferential fragmentation, typically occurring adjacent to aspartyl, glutamyl, and prolyl residues. Although these spectra have proven to be of considerable utility for database-driven protein identification, they have generally been considered to contain insufficient information to be useful for extensive de novo sequencing. Here, we report a procedure for de novo sequencing of peptides that uses MS/MS data generated by an in-house assembled MALDI-quadrupole-ion trap mass spectrometer (Krutchinsky, Kalkum, and Chait Anal. Chem. 2001, 73, 5066 -5077). Peptide sequences of up 14 amino acid residues in length have been deduced from digests of proteins separated by SDS-PAGE. Key to the success of the current procedure is an ability to obtain MS/MS spectra with high signal-to-noise ratios and to efficiently detect relatively low abundance fragment ions that result from the less favorable fragmentation pathways. The high signal-tonoise ratio yields sufficiently accurate mass differences to allow unambiguous amino acid sequence assignments (with a few exceptions), and the efficient detection of low abundance fragment ions allows continuous reads through moderately long stretches of sequence. Finally, we show how the aforementioned preferential cleavage property of singly charged ions can be used to facilitate the de novo sequencing process. T he use of mass spectrometry combined with database searching has gained wide acceptance for rapid, sensitive protein identification [1]. This method requires the availability of extensive protein, cDNA, or genomic sequence from the organism of interest (or at least from a closely related species). If such sequence information is not available, as remains the case for the vast majority of extant organisms, it is desirable to utilize de novo peptide sequencing to identify and obtain information about their protein(s). Although Edman sequencing has for a long time been a method of choice for de novo sequencing of peptides and proteins, mass spectrometry (MS) has also been shown to have considerable utility for this purpose.Indeed, mass spectrometric de novo sequencing based on the fragmentation of derivitized peptide ions dates back to the late 1960s and on underivatized peptide ions to the early 1980s (reviewed in [2] and [3]). More recently, MS sequencing has been given considerable impetus by the development of ESI and MALDI, ionization techniques whose efficiencies for producing intact peptide ions are far higher than those that were previously available. Again, both derivitized and underivatized peptides have been used in this newer work. Thus, chemical derivatization has been applied to simplify/enhance the fragmentation spectra and/or to differentiate N-from C-terminal fragment ions [4 -13]. Notable in this regard is the use of 18 O i...

show abstract

The N-CoR-HDAC3 Nuclear Receptor Corepressor Complex Inhibits the JNK Pathway through the Integral Subunit GPS2

Cited by 377 publications

References 32 publications

HDAC3: taking the SMRT-N-CoRrect road to repression

HDAC3: taking the SMRT-N-CoRrect road to repression

Class II histone deacetylases: versatile regulators

“De novo” peptide sequencing by MALDI-quadrupole-ion trap mass spectrometry: A preliminary study

Contact Info

Product

Resources

About