Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of RNA polymerase II (pol II) transcription is a highly dynamic process requiring the coordinated interaction of an array of regulatory proteins. Central to this process is the TATA-binding protein (TBP), the key component of the multiprotein complex TFIID. Interaction of TBP with core promoters nucleates the assembly of the preinitiation complex and subsequent recruitment of pol II. Despite recent advances in our understanding of the dynamic nature of the pol II transcription apparatus, the dynamics of TBP function on pol II promoters has remained largely unexplored. Human BTAF1 (TAF(II)170/TAF-172) and its yeast ortholog, Mot1p, are evolutionarily conserved members of the SNF2-like family of ATPase proteins. Genetic identification of Mot1p as a repressor of pol II transcription was supported by findings that Mot1p and BTAF1 could dissociate TBP from TATA DNA complexes using the energy of ATP hydrolysis. Recent data have revealed new aspects of BTAF1 and Mot1p as positive regulators of TBP function in the pol II system and have described new observations relating to their molecular mechanism of action. We review these data in the context of previous findings with particular attention paid to how human BTAF1 and Mot1p may dynamically regulate TBP function on pol II promoters in cells.
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PMID:Roles for BTAF1 and Mot1p in dynamics of TATA-binding protein and regulation of RNA polymerase II transcription. 1455 59

BTAF1 (formerly named TAF(II)170/TAF-172) is an essential, evolutionarily conserved member of the SNF2-like family of ATPase proteins and together with TATA-binding protein (TBP) forms the B-TFIID complex. BTAF1 has been proposed to play a key role in the dynamic regulation of TBP function in RNA polymerase II transcription. We have determined the structure of native B-TFIID purified from human cells by electron microscopy and by image analysis of single particles at a resolution of 28 A. B-TFIID is 15 x 9 nm in size and is organized into a large domain of about 170 kDa, which can be subdivided into two domains. Extending from this domain is a long thumb, which in turn is divided into subdomains of about 25, 15, and 35 kDa, the largest of which is located at the end of the thumb. Immunolabeling experiments localize the extreme carboxyl terminus of BTAF1 within the 170-kDa domain, whereas the amino terminus and TBP co-localize to the end of the protruding thumb. The central portion of BTAF1 localizes to the base of the thumb. Comparison of the native B-TFIID with its recombinant form shows that both share a similar domain organization. Collectively, these data provide the first structural model of the B-TFIID complex and map its key functional domains.
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PMID:Molecular architecture of the basal transcription factor B-TFIID. 1498 2

Transcriptional activity of the TATA-binding protein (TBP) is controlled by a variety of proteins. The BTAF1 protein (formerly known as TAF(II)170/TAF-172 and the human ortholog of Saccharomyces cerevisiae Mot1p) and the NC2 complex composed of NC2alpha (DRAP1) and NC2beta (Dr1) are able to bind to TBP directly and regulate RNA polymerase II transcription both positively and negatively. Here, we present evidence that the NC2alpha subunit interacts with BTAF1. In contrast, the NC2beta subunit is not able to associate with BTAF1 and seems to interfere with the BTAF1-TBP interaction. Addition of NC2alpha or the NC2 complex can stimulate the ability of BTAF1 to interact with TBP. This function is dependent on the presence of ATP in cell extracts but does not involve the ATPase activity of BTAF1 nor phosphorylation of NC2alpha. Together, our results constitute the first evidence of the physical cooperation between BTAF1 and NC2alpha in TBP regulation and provide a framework to understand transcription functions of NC2alpha and NC2beta in vivo.
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PMID:NC2alpha interacts with BTAF1 and stimulates its ATP-dependent association with TATA-binding protein. 1550 7

The mouse Btaf1 gene, an ortholog of yeast MOT1, encodes a highly conserved general transcription factor. The function of this SNF2-like ATPase has been studied mainly in yeast and human cells, which has revealed that it binds directly to TBP, forming the B-TFIID complex. This complex binds to core promoters of RNA polymerase II-transcribed genes and, of crucial importance, BTAF1-TBP interactions have been shown to affect the kinetics of TBP-promoter interactions. Here we report the isolation of a mouse line carrying a Btaf1 allele containing an ENU-induced point mutation that causes a substitution mutation in the BTAF1 ATPase domain. Embryos homozygous for this loss-of-function mutation appear to be morphologically normal until early somite stages, but die between embryonic days 9 and 10.5 displaying growth arrest and edema. Analyses in vitro suggest that the altered protein is less stable and, independent from this, functionally impaired in releasing of TBP from chromatin, but not in binding to TBP.
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PMID:An ENU-induced point mutation in the mouse Btaf1 gene causes post-gastrulation embryonic lethality and protein instability. 2141 21