Showing papers on "Bromodomain published in 1995"
TL;DR: Tetrahymena tubulins are modified by several types of posttranslational reactions including acetylation of alpha-tubulin at lysine 40, a modification found in most eukaryotes.
Abstract: In Tetrahymena, at least 17 distinct microtubule structures are assembled from a single primary sequence type of alpha- and beta-tubulin heterodimer, precluding distinctions among microtubular systems based on tubulin primary sequence isotypes. Tetrahymena tubulins also are modified by several types of posttranslational reactions including acetylation of alpha-tubulin at lysine 40, a modification found in most eukaryotes. In Tetrahymena, axonemal alpha-tubulin and numerous other microtubules are acetylated. We completely replaced the single type of alpha-tubulin gene in the macronucleus with a version encoding arginine instead of lysine 40 and therefore cannot be acetylated at this position. No acetylated tubulin was detectable in these transformants using a monoclonal antibody specific for acetylated lysine 40. Surprisingly, mutants lacking detectable acetylated tubulin are indistinguishable from wild-type cells. Thus, acetylation of alpha-tubulin at lysine 40 is non-essential in Tetrahymena. In addition, isoelectric focusing gel analysis of axonemal tubulin from cells unable to acetylate alpha-tubulin leads us to conclude that: (a) most or all ciliary alpha-tubulin is acetylated, (b) other lysines cannot be acetylated to compensate for loss of acetylation at lysine 40, and (c) acetylated alpha-tubulin molecules in wild-type cells contain one or more additional charge-altering modifications.
137 citations
Journal Article•
TL;DR: A new C4HC3 motif is identified in a variety of proteins including the Drosophila trithorax and its human homologue ALL-1 involved in oncogenic translocations in acute leukaemias and this domain, for which the name TTC is proposed, is found in many transcriptional regulators or DNA-binding proteins.
Abstract: Metal-binding cysteine and histidine residues are often used to stabilise a protein fold through coordination of zinc ions. These zinc fingers are either involved in nucleic acid binding (TFIIIA, GAL4, nuclear receptors, retroviral gag...) or in yet unidentified biochemical functions (LIM and RING domains). The latter characterized by a unique histidine residue in the zinc binding motif (C2HC5 and C3HC4 for the LIM and RING respectively) may constitute protein/protein interaction interfaces. We have identified a new C4HC3 motif in a variety of proteins including the Drosophila trithorax and its human homologue ALL-1 involved in oncogenic translocations in acute leukaemias. This domain, for which we propose the name TTC (for trithorax consensus) is found in many transcriptional regulators or DNA-binding proteins. Interestingly, TTC was found in several bromodomain containing transcriptional adaptors including the E1A-binding p300 and the CREB-binding CBP proteins. In CBP, this domain does not appear to be involved in DNA, CREB or TFIIB binding. In the chromosomal translocations that involve the 11q23 locus, the C-terminal end of ALL-1 (which contains 4 TTC fingers) is constantly lost. The absence of these motifs in the fusion genes may relate to their leukemogenic potential.
22 citations
TL;DR: A novel gene,brd1, has been cloned from the fission yeast Schizosaccharomyces pombe, which contains two copies of an imperfect repeat of 96 amino acid residues in its N-terminal half that include a region with high homology to the bromodomains found in transcriptional activator proteins from a diversity of eukaryotes.
Abstract: A novel gene,brd1, has been cloned from the fission yeastSchizosaccharomyces pombe. The predictedbrd1 product contains two copies of an imperfect repeat of 96 amino acid residues in its N-terminal half. These each include a region with high homology to the bromodomains found in transcriptional activator proteins from a diversity of eukaryotes. An in vivo deletion of the completebrd1 open reading frame is not lethal but cells exhibit thermosensitivity, with reductions in both cell growth and stationary phase survival at 36°C.brd1 maps adjacent to the genesuc1, but is expressed separately to give a low abundance 2.1 kb mRNA.
2 citations