Ser727-dependent recruitment of MCM5 by Stat1α in IFN-γ-induced transcriptional activation

被引:186
作者
Zhang, JJ
Zhao, YM
Chait, BT
Lathem, WW
Ritzi, M
Knippers, R
Darnell, JE
机构
[1] Rockefeller Univ, Mol Cell Biol Lab, New York, NY 10021 USA
[2] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10021 USA
[3] Univ Konstanz, Div Biol, D-78434 Constance, Germany
关键词
interferon; MCM5; Stat1; transcription;
D O I
10.1093/emboj/17.23.6963
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
Stat1 alpha is a latent cytoplasmic transcription factor activated in response to interferon-gamma (IFN-gamma). The C-terminal 38 amino acids of Stat1 alpha are required to trigger transcription and therefore may possibly serve as a transcription activation domain (TAD), Here we show that the C-terminus of Stat1 alpha is an independent TAD which can interact with a specific group of nuclear proteins. Mutation of the Stat1 Ser727 and Leu724 decreases its transcriptional activity and affinity for the nuclear proteins. One of the interacting proteins was identified as MCMS, a member of the minichromosome maintenance (MCM) family involved in DNA replication, Both in vitro and in vivo interaction of Stat1 alpha and MCMS were demonstrated. Furthermore, the in vitro interaction required Ser727 and was enhanced by its phosphorylation, transient overexpression of MCMS enhanced transcriptional activation by Stat1 alpha in a Ser727-dependent manner. Finally, changes in the level of nuclear localized MCMS during the cell cycle correlated with the changes in transcriptional response to IFN-gamma lacting through Stat1 alpha. These results strongly suggest that MCM5 is recruited through interaction with Stat1 alpha in a Ser727- and Leu724-dependent manner to play a role in optimal transcriptional activation.
引用
收藏
页码:6963 / 6971
页数:9
相关论文
共 51 条
  • [1] Components and dynamics of DNA replication complexes in S-cerevisiae: Redistribution of MCM proteins and Cdc45p during S phase
    Aparicio, OM
    Weinstein, DM
    Bell, SP
    [J]. CELL, 1997, 91 (01) : 59 - 69
  • [2] Polymerases and the replisome: Machines within machines
    Baker, TA
    Bell, SP
    [J]. CELL, 1998, 92 (03) : 295 - 305
  • [3] Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha
    Bhattacharya, S
    Eckner, R
    Grossman, S
    Oldread, E
    Arany, Z
    DAndrea, A
    Livingston, DM
    [J]. NATURE, 1996, 383 (6598) : 344 - 347
  • [4] Mediator of transcriptional regulation
    Bjorklund, S
    Kim, YJ
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (09) : 335 - 337
  • [5] Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma
    Bromberg, JF
    Horvath, CM
    Wen, ZL
    Schreiber, RD
    Darnell, JE
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) : 7673 - 7678
  • [6] Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to DNA
    Chen, XM
    Vinkemeier, U
    Zhao, YX
    Jeruzalmi, D
    Darnell, JE
    Kuriyan, J
    [J]. CELL, 1998, 93 (05) : 827 - 839
  • [7] JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS
    DARNELL, JE
    KERR, IM
    STARK, GR
    [J]. SCIENCE, 1994, 264 (5164) : 1415 - 1421
  • [8] STATs and gene regulation
    Darnell, JE
    [J]. SCIENCE, 1997, 277 (5332) : 1630 - 1635
  • [9] CYTOPLASMIC ACTIVATION OF GAF, AN IFN-GAMMA-REGULATED DNA-BINDING FACTOR
    DECKER, T
    LEW, DJ
    MIRKOVITCH, J
    DARNELL, JE
    [J]. EMBO JOURNAL, 1991, 10 (04) : 927 - 932
  • [10] Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast
    Donovan, S
    Harwood, J
    Drury, LS
    Diffley, JFX
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (11) : 5611 - 5616