Disease relevance of PBRM1

• Thus, BAF180 is a strong candidate TSG for lung cancer [1].
• Finally, we found no amino-acid sequence coding mutations in five non-small-cell and five small-cell lung cancer cell lines, while we did find a new splicing isoform of BAF180 (AY281068) [1].
• BAF180 can be mutated and has tumor suppressing properties in breast cancer [1].
• The hPB1 gene is located on chromosome 3p21, where the tumor suppressor genes for breast, lung and kidney cancers have been mapped [2].
• The RNA-dependent RNA polymerase of influenza virus is a heterotrimer formed by the PB1, PB2, and PA subunits [3].

High impact information on PBRM1

• The selectivity by PBAF requires a novel subunit, BAF200, but not the previously described PBAF-specificity subunit, BAF180 (Polybromo) [4].
• The PB1 domain and the PC motif-containing region are structurally similar protein binding modules [5].
• Endonuclease cleavage, which is activated by the subsequent binding of the 3' terminal sequence of vRNA, resides in a PB1 sequence that contains three essential acidic amino acids, similar to the active sites of other enzymes that cut polynucleotides to produce 3'-OH ends [6].
• We report here the NMR structure and ligand-binding site of the PB1 domain of the cell polarity establishment protein, Bem1p [7].
• The chemical shift perturbation experiment and the mutagenesis study show that the PC motif is a major structural element that binds to the PB1 domain [7].

Chemical compound and disease context of PBRM1

• Despite being isolated within a single year in the same geographical location, human H5N1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [PB2, PB1, PA and nucleoprotein (NP)] as well as the matrix (M) proteins 1 and 2 and nonstructural (NS) proteins 1 and 2 [8].
• We have demonstrated that 5'-capped short RNA fragments inhibit the expression of chloramphenicol acetyltransferase (CAT) in the murine 76 cell line, derived which expresses the genes for the RNA polymerases (PB1, PB2, and PA) and the nucleoprotein (NP) of influenza virus in response to treatment with dexamethasone [9].
• In this study, we obtained partial gene sequences of 4 genes (PB1-like protein, PA-like protein, glycoprotein, and nucleoprotein) of 8 Thogoto virus strains isolated in Africa, Asia, and Europe and studied the genetic variation and phylogeny [10].

Biological context of PBRM1

• Computational analysis reveals six tandem bromodomains within the amino-terminal region of the human Polybromo-1 protein, a required subunit of the Polybromo, BRG1-associated factors chromatin remodeling complex [11].
• Immunofluorescence studies with a BAF180 antibody revealed that SWI/SNF-B localizes at the kinetochores of chromosomes during mitosis [12].
• The 3p21 candidate tumor suppressor gene BAF180 is normally expressed in human lung cancer [1].
• The objective of this study was to determine whether BAF180 mRNA or protein expression was inactivated or abnormal in lung cancers to prompt detailed DNA promoter methylation or mutational analyses [1].
• cDNA cloning of the human polybromo-1 gene on chromosome 3p21 [2].

Anatomical context of PBRM1

• Mass spectrometric analysis, and immunoblotting with antibodies specific to hOsa1 or hOsa2 demonstrate the presence of both proteins in SWI/SNF-A but not in the related polybromo-BRG1-associated factors complex purified from HeLa cells [13].
• The PB1-F2 protein of Influenza A virus: increasing pathogenicity by disrupting alveolar macrophages [14].
• Here we identify a novel domain PB1 in the budding yeast protein Bem1p, which functions in polarity establishment, and mammalian p67(phox), which activates the microbicidal phagocyte NADPH oxidase [15].
• In this report, we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells [16].
• Here we demonstrate that both PB1 and PB2 are required for targeting the catalytic activity of Plk1 to centrosomes, midbody, and kinetochores [17].

Associations of PBRM1 with chemical compounds

• In addition to the PB2 protein subunit acquiring the ability to bind 5'-capped ends of RNAs, the PB1 protein itself acquires the ability to bind the 3' sequence of vRNA, via a ribonucleoprotein 1 (RNP1)-like motif, amino acids 249-256, which contains two phenylalanine residues required for binding [18].
• On the interface, several salt bridges are formed including the conserved acidic residues on the OPCA motif of PKCiota PB1 and the conserved lysine residue on the Par6alpha PB1 [19].
• Sucrose density gradient analysis showed that the P protein complexes ranged from about 11S to 22S and that almost all of the PB1 and PB2 protein molecules synthesized during a 1-h period (2.5 to 3.5 h postinfection) were in these complexes [20].
• Mutant PAS509, which had a serine insertion at position 509, bound to PB1 like wild-type PA but did not show any polymerase activity [21].
• The neuraminidase (NA) and PB1 genes of the H1N2 isolate were of human origin, while the hemagglutinin (HA), matrix (M), nucleoprotein (NP), and non-structural (NS) genes were of swine origin and PA and PB2 gene were of avain origin [22].

Other interactions of PBRM1

• Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice [23].
• This paper recalls the reasons why growth models are useful, analyses briefly the structure and the characteristics of the two fundamental human growth functions, i.e. triple-logistic and PB1, and shows how the use of PB1 model may be extended also to impaired growth, e.g. in girls with Turner syndrome [24].

Analytical, diagnostic and therapeutic context of PBRM1

• Individual bromodomains from Polybromo-1 were cloned from human cDNA into a pET30b expression vector enabling effective one-step purification by affinity chromatography [11].
• In 30 non-small-cell and 26 small-cell lung cancer cell lines, most of which had 3p21 allele loss, BAF180 mRNA and protein expression were evaluated by RT-PCR using three sets of primers and Western blotting using two anti-BAF180 antibodies [1].
• Northern blot analysis detected the ubiquitous expression of hPB1 mRNA in a variety of human tissues [2].
• Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors [16].
• The cytoplasmic and nuclear extracts from infected cells were depleted of nucleocapsids by centrifugation, and the resulting supernatants were subjected to immunoprecipitation with an antiserum specific for either the PB1 protein or the PB2 protein [20].

References