Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maximal human immunodeficiency virus type 1 (HIV-1) gene expression requires specific cellular factors in addition to the virus-encoded trans-activator protein Tat and the RNA element TAR. We developed a functional assay, based on transcriptional activation in vitro, to identify these cellular factors. Here, we describe the purification and molecular cloning of CA150, a nuclear protein that is associated with the human RNA polymerase II holoenzyme and is involved in Tat-dependent HIV-1 transcriptional activation. The sequence of CA150 contains an extensive glutamine- and alanine-rich repeat that is found in transcriptional modulators such as GAL11 and SSN6 in Saccharomyces cerevisiae and Zeste in Drosophila melanogaster. Immunodepletion of CA150 abolished Tat trans activation in vitro. Moreover, overexpression of a mutant CA150 protein specifically and dramatically decreased Tat-mediated activation of the HIV-1 promoter in vivo, strongly suggesting a role for CA150 in HIV-1 gene regulation. Immunoprecipitation experiments demonstrated that both CA150 and Tat associate with the RNA polymerase II holoenzyme. Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150.
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PMID:CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription. 931 62

Tat protein strongly activates transcription from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by enhancing the elongation efficiency of RNA polymerase II complexes. Tat-mediated transcriptional activation requires cellular cofactors and specific cis-acting elements within the HIV-1 promoter, among them a functional TATA box. Here, we have investigated the mechanism by which one of these cofactors, termed CA150, regulates HIV-1 transcription in vivo. We present a series of functional assays that demonstrate that the regulation of the HIV-1 LTR by CA150 has the same functional requirements as the activation by Tat. We found that CA150 affects elongation of transcription complexes assembled on the HIV-1 promoter in a TATA-box-dependent manner. We discuss the data in terms of the involvement of CA150 in the regulation of Tat-activated HIV-1 gene expression. In addition, we also provide evidence suggesting a role for CA150 in the regulation of cellular transcriptional processes.
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PMID:Transcriptional cofactor CA150 regulates RNA polymerase II elongation in a TATA-box-dependent manner. 1037 21

We previously characterized p144 bearing N-acetylglucosamine residues in a rat liver nuclear matrix fraction. Based on partial amino acid sequences of rat p144, mouse p144 cDNA was cloned and sequenced, and its amino acid sequence was predicted. The sequence revealed that p144 is a rat homologue of CA150, which is a transcription factor involved in Tat-activated human immunodeficiency virus type 1 transcription. The reported human CA150 consists of 1098 amino acids and has a leucine zipper-like motif in its carboxyl-region. However, a clone of mouse p144 cDNA encoded a CA150 consisting of 1,034 amino acids. The mouse CA150 was shorter by 64 amino acids than hitherto known human CA150 and lacked the leucine zipper-like motif. We designated the longer and shorter CA150 species as CA150a and CA150b, respectively. The partial nucleotide sequences of other mouse p144 cDNA clones were examined and it was found that some clones encode CA150a having a leucine zipper-like motif. It was suggested that CA150a and CA150b are splicing isoforms. All rat and mouse tissues examined contained transcripts for both CA150a and CA150b. Both transcripts were detected in human blood and Jurkat cells as well as mouse CD4(+) T-cells, which are the HIV-1-sensitive counterpart in humans.
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PMID:Molecular cloning and splicing isoforms of mouse p144, a homologue of CA150. 1057 54

The human transcription factor CA150 modulates human immunodeficiency virus type 1 gene transcription and contains numerous signaling elements, including six FF domains. Repeated FF domains are present in several transcription and splicing factors and can recognize phosphoserine motifs in the C-terminal domain (CTD) of RNA polymerase II (RNAPII). Using mass spectrometry, we identify a number of nuclear binding partners for the CA150 FF domains and demonstrate a direct interaction between CA150 and Tat-SF1, a protein involved in the coupling of splicing and transcription. CA150 FF domains recognize multiple sites within the Tat-SF1 protein conforming to the consensus motif (D/E)(2/5)-F/W/Y-(D/E)(2/5). Individual FF domains are capable of interacting with Tat-SF1 peptide ligands in an equivalent and noncooperative manner, with affinities ranging from 150 to 500 microM. Repeated FF domains therefore appear to bind their targets through multiple weak interactions with motifs comprised of negatively charged residues flanking aromatic amino acids. The RNAPII CTD represents a consensus FF domain-binding site, contingent on generation of the requisite negative charges by phosphorylation of serines 2 and 5. We propose that CA150, through the dual recognition of acidic motifs in proteins such as Tat-SF1 and the phosphorylated CTD, could mediate the recruitment of transcription and splicing factors to actively transcribing RNAPII.
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PMID:FF domains of CA150 bind transcription and splicing factors through multiple weak interactions. 1548 97