Abstract:
:Gamma interferon (IFN-γ) is an inflammatory cytokine that has complex effects on myogenesis. Here, we show that the IFN-γ-induced inhibition of myogenesis is mediated by the major histocompatibility complex (MHC) class II transactivator, CIITA, which binds to myogenin and inhibits its activity. In IFN-γ-treated myoblasts, the inhibition of muscle-specific genes includes the expression of myogenin itself, while in myotubes, myogenin expression is unaffected. Thus, CIITA appears to act by both repressing the expression and inhibiting the activity of myogenin at different stages of myogenesis. Stimulation by IFN-γ in skeletal muscle cells induces CIITA expression as well as MHC class II gene expression. The IFN-γ-mediated repression is reversible, with myogenesis proceeding normally upon removal of IFN-γ. Through overexpression studies, we confirm that the expression of CIITA, independent of IFN-γ, is sufficient to inhibit myogenesis. Through knockdown studies, we also demonstrate that CIITA is necessary for the IFN-γ-mediated inhibition of myogenesis. Finally, we show that CIITA, which lacks DNA binding activity, is recruited to muscle-specific promoters coincident with reductions in RNA polymerase II recruitment. Thus, this work reveals how IFN-γ modulates myogenesis and demonstrates a key role for CIITA in this process.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Londhe P,Davie JKdoi
10.1128/MCB.05397-11subject
Has Abstractpub_date
2011-07-01 00:00:00pages
2854-66issue
14eissn
0270-7306issn
1098-5549pii
MCB.05397-11journal_volume
31pub_type
杂志文章abstract::XPC is responsible for DNA damage sensing in nucleotide excision repair (NER). Mutations in XPC lead to a defect in NER and to xeroderma pigmentosum (XP-C). Here, we analyzed the biochemical properties behind mutations found within three patients: one amino acid substitution (P334H, XP1MI, and GM02096), one amino acid...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00781-08
更新日期:2008-12-01 00:00:00
abstract::Simian virus 40 (SV40) large tumor antigen (T antigen) has been shown to inhibit p53-dependent transcription by preventing p53 from binding to its cognate cis element. Data presented in this report provide the first direct functional evidence that T antigen, under certain conditions, may also repress p53-dependent tra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.2746
更新日期:1999-04-01 00:00:00
abstract::The human and murine MOK2 ortholog genes that are preferentially expressed in brain and testis tissues encode two different Krüppel-like zinc finger proteins. In this paper, we show that the MOK2 proteins are mainly associated with nuclear ribonucleoprotein components, including the nucleoli and extranucleolar structu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.4.2116
更新日期:1997-04-01 00:00:00
abstract::During the functional analysis of open reading frames (ORFs) identified during the sequencing of chromosome III of Saccharomyces cerevisiae, the previously uncharacterized ORF YCL031C (now designated RRP7) was deleted. RRP7 is essential for cell viability, and a conditional null allele was therefore constructed, by pl...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.9.5023
更新日期:1997-09-01 00:00:00
abstract::Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in MEKs that are regulated by Raf family enzymes but is missing from MEKs and...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.10.5214
更新日期:1995-10-01 00:00:00
abstract::Members of the cytokine receptor superfamily have structurally similar extracellular ligand-binding domains yet diverse cytoplasmic regions lacking any obvious catalytic domains. Many of these receptors form ligand-induced oligomers which are likely to participate in transmembrane signaling. A constitutively active (f...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.3535
更新日期:1994-06-01 00:00:00
abstract::The ubiquitin proteolytic system plays a major role in a variety of basic cellular processes. In the majority of these processes, the target proteins are completely degraded. In one exceptional case, generation of the p50 subunit of the transcriptional regulator NF-kappaB, the precursor protein p105 is processed in a ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.5.3664
更新日期:1999-05-01 00:00:00
abstract::Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.7.3929
更新日期:1993-07-01 00:00:00
abstract::Eukaryotic mRNA translation begins with recruitment of the 40S ribosome complex to the mRNA 5' end through the eIF4F initiation complex binding to the 5' m(7)G-mRNA cap. Spliced leader (SL) RNA trans splicing adds a trimethylguanosine (TMG) cap and a sequence, the SL, to the 5' end of mRNAs. Efficient translation of T...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01437-09
更新日期:2010-04-01 00:00:00
abstract::The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells)....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.10.6452
更新日期:1994-10-01 00:00:00
abstract::In Saccharomyces cerevisiae, COX5a and COX5b encode two distinct forms of cytochrome c oxidase subunit V, Va and Vb, respectively. To determine the relative contribution of COX5a and COX5b to cytochrome c oxidase function, we have disrupted each gene. Cytochrome c oxidase activity levels and respiration rates of strai...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.10.3520
更新日期:1987-10-01 00:00:00
abstract::A new family of highly conserved genes, designated rho, has recently been isolated and characterized (P. Madaule and R. Axel, Cell 41:31-40, 1985). These genes have been found in Saccharomyces cerevisiae, Drosophila melanogaster, rats, and humans, and their 21,000-dalton products are highly homologous. The rho p21 pro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.10.3620
更新日期:1987-10-01 00:00:00
abstract::To understand the mechanism of retinoid resistance, we studied the subcellular localization and function of retinoid receptors in human breast cancer cell lines. Retinoid X receptor alpha (RXR alpha) localized throughout the nucleoplasm in retinoid-sensitive normal human mammary epithelial cells and in retinoid-respon...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.9.3972-3982.2004
更新日期:2004-05-01 00:00:00
abstract::The chimeric oncoprotein E2A-HLF, generated by the t(17;19) chromosomal translocation in pro-B-cell acute lymphoblastic leukemia, incorporates the transactivation domains of E2A and the basic leucine zipper (bZIP) DNA-binding and protein dimerization domain of HLF (hepatic leukemic factor). The ability of E2A-HLF to p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.10.6035
更新日期:1998-10-01 00:00:00
abstract::Budding yeast Rad53 is an essential protein kinase that is phosphorylated and activated in a MEC1- and TEL1-dependent manner in response to DNA damage. We studied the role of Rad53 phosphorylation through mutation of consensus phosphorylation sites for upstream kinases Mec1 and Tel1. Alanine substitution of the Rad53 ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.17.6300-6314.2003
更新日期:2003-09-01 00:00:00
abstract::High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.6.3147
更新日期:1995-06-01 00:00:00
abstract::Fragments of African green monkey (Cercopithecus aethiops) DNA (3.5 to 18.0 kilobases) were inserted downstream from the thymidine kinase (TK, tk) coding region in pTK206/SV010, a gene construct which lacks both copies of the hexanucleotide 5'-AATAAA-3' and contains a simian virus 40 origin of replication, allowing it...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.4.643
更新日期:1983-04-01 00:00:00
abstract::The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth fa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00552-06
更新日期:2006-08-01 00:00:00
abstract::We identified Ras guanine-releasing protein 3 (RasGRP3) as a guanine exchange factor expressed in blood vessels via an embryonic stem (ES) cell-based gene trap screen to identify novel vascular genes. RasGRP3 is expressed in embryonic blood vessels, down-regulated in mature adult vessels, and reexpressed in newly form...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.24.10515-10528.2004
更新日期:2004-12-01 00:00:00
abstract::As a subunit of a ubiquitin ligase, Skp2 is implicated in facilitating cell cycle progression via degradation of various protein targets. We report here that Skp2 is rapidly degraded following cellular stimulation by the cytokine transforming growth factor beta (TGF-beta) and that this degradation stabilizes the cell ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01830-06
更新日期:2007-04-01 00:00:00
abstract::The formation of inosine at the wobble position of eukaryotic tRNAs is an essential modification catalyzed by the ADAT2/ADAT3 complex. In humans, a valine-to-methionine mutation (V144M) in ADAT3 that originated ∼1,600 years ago is the most common cause of autosomal recessive intellectual disability (ID) in Arabia. Whi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00203-19
更新日期:2019-09-11 00:00:00
abstract::Mitochondrial respiratory complexes of the electron transport chain (CI, CIII, and CIV) can be assembled into larger structures forming supercomplexes. We analyzed the assembly/stability of respiratory complexes in mouse lung fibroblasts lacking the Rieske iron-sulfur protein (RISP knockout [KO]cells), one of the cata...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06051-11
更新日期:2012-01-01 00:00:00
abstract::In this report, we explored the mechanisms underlying keratinocyte-specific and differentiation-specific gene expression in the skin. We have identified five keratinocyte-specific, open chromatin regions that exist within the 6 kb of 5' upstream regulatory sequence known to faithfully recapitulate the strong endogenou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.12.4293-4308.2002
更新日期:2002-06-01 00:00:00
abstract::Protein phosphatase 2A (PP2A) is a multimeric serine/threonine phosphatase that carries out multiple functions. Although numerous observations suggest that PP2A plays a major role in downregulation of the mitogen-activated protein (MAP) kinase pathway, the precise mechanisms are unknown. To clarify the role of PP2A in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.7.2375-2387.2002
更新日期:2002-04-01 00:00:00
abstract::Interferon (IFN) regulatory factor 1 (IRF-1) and IRF-2 were originally identified as transcription factors involved in the regulation of the IFN system. IRF-1 functions as a transcriptional activator, while IRF-2 represses IRF-1 function. More recently, evidence has been provided that IRF-1 and IRF-2 manifest antionco...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.8.4531
更新日期:1993-08-01 00:00:00
abstract::Tumor suppressor genes regulate the antiviral host defense through molecular mechanisms that are not yet well explored. Here, we show that the tumor suppressor retinoblastoma (Rb) protein positively regulates Toll-like receptor 3 (TLR3) expression, the sensing receptor for viral double-stranded RNA and poly(I · C). TL...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06454-11
更新日期:2012-04-01 00:00:00
abstract::Drosophila melanogaster telomeres have two DNA domains: a terminal array of retrotransposons and a subterminal repetitive telomere-associated sequence (TAS), a source of telomere position effect (TPE). We reported previously that deletion of the 2L TAS array leads to dominant suppression of TPE by stimulating in trans...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00515-07
更新日期:2007-07-01 00:00:00
abstract::The homeobox gene HOXA9 has recently been shown to be an important regulator of endothelial cell (EC) differentiation and activation in addition to its role in embryonic development and hematopoiesis. In this report, we have determined that the EC-leukocyte adhesion molecule E-selectin is a key target for HOXA9. The d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00052-07
更新日期:2007-06-01 00:00:00
abstract::We have previously shown that Saccharomyces cerevisiae Isw2 complex slides nucleosomes to remodel chromatin in vivo. Our data suggested a model in which Isw2 complex binds the histone octamer and DNA separately to generate the force necessary for nucleosome movement. Here we find that the histone H4 "basic patch" is t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.21.9165-9174.2005
更新日期:2005-11-01 00:00:00
abstract::Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.4.1846
更新日期:1992-04-01 00:00:00