A single amino acid change converts an inhibitory transcription factor into an activator

被引:29
作者
Dawson, SJ [1 ]
Morris, PJ [1 ]
Latchman, DS [1 ]
机构
[1] UCL, SCH MED, MED MOLEC BIOL UNIT, DEPT MOLEC PATHOL, LONDON W1P 6DB, ENGLAND
关键词
D O I
10.1074/jbc.271.20.11631
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The closely related POU family transcription factors Brn-3a and Brn-3b differ in their functional activity with Brn-3a activating several target promoters, which are repressed by Brn-3b. Brn-3b also prevents promoter activation by Brn-3a. Here we have altered a single isoleucine residue in the POU homeodomain of Brn-3b to the valine residue found at the equivalent position in Brn-3a. This change not only abolishes the ability of Brn-3b to repress basal and Brn-3a-stimulated promoter activity but also converts it to an activator of similar potency to Brn-3a. Hence a single amino acid difference determines the difference between an activator and a repressor in the Brn-3 family.
引用
收藏
页码:11631 / 11633
页数:3
相关论文
共 27 条
  • [1] A PROCEDURE TO STANDARDIZE CAT REPORTER GENE ASSAY
    ABKEN, H
    REIFENRATH, B
    [J]. NUCLEIC ACIDS RESEARCH, 1992, 20 (13) : 3527 - 3527
  • [2] BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
  • [3] The different activities of the two activation domains of the Brn-3a transcription factor are dependent on the context of the binding site
    BudhramMahadeo, V
    Morris, PJ
    Lakin, ND
    Dawson, SJ
    Latchman, DS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (15) : 9108 - 9113
  • [4] ACTIVATION OF THE ALPHA-INTERNEXIN PROMOTER BY THE BRN-3A TRANSCRIPTION FACTOR IS DEPENDENT ON THE N-TERMINAL REGION OF THE PROTEIN
    BUDHRAMMAHADEO, V
    MORRIS, PJ
    LAKIN, ND
    THEIL, T
    CHING, GY
    LILLYCROP, KA
    MOROY, T
    LIEM, RKH
    LATCHMAN, DS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (06) : 2853 - 2858
  • [5] THE DNA TARGET SITE FOR THE BRN-3 POU FAMILY TRANSCRIPTION FACTORS CAN CONFER RESPONSIVENESS TO CYCLIC-AMP AND REMOVAL OF SERUM IN NEURONAL CELLS
    BUDHRAMMAHADEO, V
    THEIL, T
    MORRIS, PJ
    LILLYCROP, KA
    MOROY, T
    LATCHMAN, DS
    [J]. NUCLEIC ACIDS RESEARCH, 1994, 22 (15) : 3092 - 3098
  • [6] The ability of POU family transcription factors to activate or repress gene expression is dependent on the spacing and context of their specific response elements
    Dawson, SJ
    Liu, YZ
    Rodel, B
    Moroy, T
    Latchman, DS
    [J]. BIOCHEMICAL JOURNAL, 1996, 314 : 439 - 443
  • [7] A GENETIC PATHWAY FOR THE DEVELOPMENT OF THE CAENORHABDITIS-ELEGANS HSN MOTOR NEURONS
    DESAI, C
    GARRIGA, G
    MCINTIRE, SL
    HORVITZ, HR
    [J]. NATURE, 1988, 336 (6200) : 638 - 646
  • [8] BRN-3.0 EXPRESSION IDENTIFIES EARLY POSTMITOTIC CNS NEURONS AND SENSORY NEURAL PRECURSORS
    FEDTSOVA, NG
    TURNER, EE
    [J]. MECHANISMS OF DEVELOPMENT, 1995, 53 (03) : 291 - 304
  • [9] THE C-ELEGANS CELL LINEAGE AND DIFFERENTIATION GENE UNC-86 ENCODES A PROTEIN WITH A HOMEODOMAIN AND EXTENDED SIMILARITY TO TRANSCRIPTION FACTORS
    FINNEY, M
    RUVKUN, G
    HORVITZ, HR
    [J]. CELL, 1988, 55 (05) : 757 - 769
  • [10] BRN-3.0 - A POU-DOMAIN PROTEIN EXPRESSED IN THE SENSORY, IMMUNE, AND ENDOCRINE SYSTEMS THAT FUNCTIONS ON ELEMENTS DISTINCT FROM KNOWN OCTAMER MOTIFS
    GERRERO, MR
    MCEVILLY, RJ
    TURNER, E
    LIN, CR
    OCONNELL, S
    JENNE, KJ
    HOBBS, MV
    ROSENFELD, MG
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) : 10841 - 10845