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

Jue J. Zhang, Yingming Zhao, Brian T. Chait, Wyndham W. Lathem, Marion Ritzi, Rolf Knippers, James E. Darnell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

Abstract

Stat1α is a latent cytoplasmic transcription factor activated in response to interferon-γ (IFN-γ). The C-terminal 38 amino acids of Stat1α are required to trigger transcription and therefore may possibly serve as a transcription activation domain (TAD). Here we show that the C-terminus of Stat1α 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 MCM5, a member of the mini-chromosome maintenance (MCM) family involved in DNA replication. Both in vitro and in vivo interaction of Stat1α and MCM5 were demonstrated. Furthermore, the in vitro interaction required Ser727 and was enhanced by its phosphorylation. Transient over-expression of MCM5 enhanced transcriptional activation by Stat1α in a Ser727-dependent manner. Finally, changes in the level of nuclear localized MCM5 during the cell cycle correlated with the changes in transcriptional response to IFN-γ acting through Stat1α. These results strongly suggest that MCM5 is recruited through interaction with Stat1α in a Ser727- and Leu724-dependent manner to play a role in optimal transcriptional activation.

Original languageEnglish (US)
Pages (from-to)6963-6971
Number of pages9
JournalEMBO Journal
Volume17
Issue number23
DOIs
StatePublished - Dec 1 1998

Keywords

  • Interferon
  • MCM5
  • Stat1
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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