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)

We have sequenced a gene that encodes a 377 amino acid putative protein with an ATPase motif typical of the protein family including SEC18p (NSF = N-ethyl maleimide-sensitive fusion protein; vesicle-mediated endoplasmic reticulum to Golgi protein transfer), PAS1p (peroxisome assembly), CDC48p (VCP = valosin-containing protein; cell cycle) and TBP1 (Tat-binding protein). This gene, AFG1 for ATPase family gene, also has substantial homology to these proteins outside the ATPase domain. AFG1 is located on chromosome V immediately centromere-proximal to MAK10.
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PMID:AFG1, a new member of the SEC18-NSF, PAS1, CDC48-VCP, TBP family of ATPases. 144 55

We have characterized a newly identified gene from Dictyostelium discoideum, DdTBP alpha, that encodes a member of the family of eukaryotic proteins. These proteins contain a conserved ATPase domain, include subunits of the 26S protease subunit, and are homologous to the mammalian human immunodeficiency virus Tat-binding protein TBP1. While information indicates that some family members are involved in the regulation of transcription in mammalian and yeast cells during growth, these proteins are also involved in other cellular functions, and nothing is known about their possible function in multicellular development. The Dictyostelium DdTBP alpha gene is developmentally regulated, with its expression at the highest levels occurring during growth and early development. The gene is present in two copies in the genome. Disruption of one copy by homologous recombination leads to aberrant morphogenesis, which lasts from the formation of the first finger until the onset of culmination. The gene appears to be essential for growth since we were unable to obtain a complete null phenotype and since expression of an inducible antisense construct in the partial null background resulted in cell death. Expression of the antisense construct during development accentuated the partial null phenotype and also resulted in very abnormal fruiting bodies. Overexpression of DdTBP alpha from its own promoter leads to very large multinucleated vegetative cells when the cells are grown in suspension culture. When the cells are plated onto petri dishes in growth medium, they rapidly split into multiple cells containing one to two nuclei, in a manner similar to that of wild-type cells. Overexpressing cells are significantly delayed in forming a multicellular aggregate, but development proceeds normally once the first finger stage is reached. The results indicate that DdTBP alpha plays an important role in regulating both growth and morphogenesis in D. discoideum.
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PMID:Growth and developmental functions of a human immunodeficiency virus Tat-binding protein/26S protease subunit homolog from Dictyostelium discoideum. 786 64

von Hippel-Lindau (VHL) gene inactivation occurs in von Hippel-Lindau (VHL) disease. The protein pVHL functions in a multi-subunit E3 ubiquitin ligase that targets the hypoxia-inducible transcription factor Hif1 alpha for proteasomal degradation during normoxia. We establish that pVHL binds to Tat-binding protein-1 (TBP-1), a component of the 19S regulatory complex of the proteasome. TBP-1 associates with the beta-domain of pVHL and complexes with pVHL and Hif1 alpha in vivo. Overexpression of TBP-1 promotes degradation of Hif1 alpha in a pVHL-dependent manner that requires the ATPase domain of TBP-1. Blockade of TBP-1 expression by small interfering RNA (siRNA) causes prolonged degradation kinetics of Hif1 alpha. Several distinct mutations in exon 2 of VHL disrupt binding of pVHL to TBP-1. A pVHL mutant containing a P154L substitution coimmunoprecipitates with Hif1 alpha, but not TBP-1, and does not promote degradation of Hif1 alpha. Thus, the ability of pVHL to degrade Hif1 alpha depends in part on its interaction with TBP-1 and suggests a new mechanism for Hif1 alpha stabilization in some pVHL-deficient tumors.
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PMID:Tat-binding protein-1, a component of the 26S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel-Lindau protein. 1455 7

The 26S proteasome, which degrades ubiquitinated proteins, appears to contribute to the cyclical loading of androgen receptor (AR) to androgen response elements of target gene promoters; however, the mechanism whereby the 26S proteasome modulates AR recruitment remains unknown. Using yeast two-hybrid screening, we previously identified Tat-binding protein-1 (TBP-1), an adenosine triphosphatase of 19S regulatory particles of the 26S proteasome, as a transcriptional coactivator of thyroid hormone receptor. Independently, TBP-1-interacting protein (TBPIP) was also identified as a coactivator of several nuclear receptors, including AR. Here, we investigated whether TBP-1 could interact with and modulate transcriptional activation by AR cooperatively with TBPIP. TBP-1 mRNA was ubiquitously expressed in human tissues, including the testis and prostate, as well as in LNCaP cells. TBP-1 directly bound TBPIP through the amino-terminal domain possessing the leucine zipper structure. AR is physically associated with TBP-1 and TBPIP in vitro and in LNCaP cells. TBP-1 similarly and additively augmented AR-mediated transcription upon coexpression with TBPIP, and the ATPase domain, as well as leucine zipper structure in TBP-1, was essential for transcriptional enhancement. Overexpression of TBP-1 did not alter AR protein and mRNA levels. In the chromatin immunoprecipitation assay, TBP-1 was transiently recruited to the proximal androgen response element of the prostate-specific antigen gene promoter in a ligand-dependent manner in LNCaP cells. These findings suggest that a component of 19S regulatory particles directly binds AR and might participate in AR-mediated transcriptional activation in cooperation with TBPIP.
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PMID:Tat-binding protein-1 (TBP-1), an ATPase of 19S regulatory particles of the 26S proteasome, enhances androgen receptor function in cooperation with TBP-1-interacting protein/Hop2. 1932 2

19S regulatory particles (19SRP) of 26S proteasome participate in multiple steps of gene transcription in yeast. We previously showed that Tat-binding protein-1 (TBP-1), an ATPase of 19SRP, interacts with thyroid hormone receptor (TR) and enhances TR-mediated transcription synergistically with steroid receptor coactivator-1 (SRC-1). To further elucidate the roles of ATPases and a non-ATPase component of 19SRP in gene regulation by TR, we investigated whether knockdown (KO) of TBP-1, TRIP1 or Rpn10 using small interfering RNA affects TR-mediated transactivation in HeLa cells. KO of individual subunits attenuated TR-mediated transactivation through the thyroid hormone response element (TRE) in the absence or presence of cotransfected SRC-1 without altering TR and SRC-1 protein levels. KO of TBP-1 disrupted ligand-induced loading of TR, SRC-1, and RNA polymerase II in chromatin immunoprecipitation assays. Collectively, both ATPase and non-ATPase components of 19SRP play critical roles in TR-mediated transactivation by coordinating the proper loading of liganded TR to TRE.
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PMID:Roles of proteasomal 19S regulatory particles in promoter loading of thyroid hormone receptor. 1955 66

Class II transactivator (CIITA) is the master regulator of the major histocompatibility class II transcription complex (MHC-II) and is critical for initiation of adaptive immune responses. We have previously demonstrated that the 19S proteasome ATPase Sug1 plays a significant role in regulating CIITA activity and MHC-II expression. We now show that an additional component of the 19S complex, the 19S ATPase S6a (S6'/Tat-binding protein 1), is crucial for regulating cytokine-inducible transcription of CIITA. Lack of S6a negatively impacts CIITA activity and CIITA expression. Decreased expression of S6a significantly diminishes the recruitment of transcription factors to the CIITA interferon-gamma-inducible promoter [CIITA promoter IV (pIV)] and significantly decreases CIITApIV histone H3 and histone H4 acetylation, with a preferential loss of acetylation at H3 lysine 18 and H4 lysine 8. In addition, we provide evidence for the involvement of the 19S AAA (ATPases associated with diverse cellular activity) ATPase hexamer as the 19S ATPase S6b binds CIITApIV in an S6a-dependent fashion and has effects similar to S6a on CIITApIV histone acetylation. These analyses demonstrate the importance of 19S ATPases in the assembly of CIITApIV transcription machinery and provide additional insight into the regulatory mechanisms of the 19S proteasome in mammalian transcription.
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PMID:The 19S ATPase S6a (S6'/TBP1) regulates the transcription initiation of class II transactivator. 1985 14