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- Title
Ser727-dependent recruitment of MCM5 by Stat1a in IFN-?-induced transcriptional activation.
- Authors
Zhang, Jue J.; Yingming Zhao; Chait, Brian T.; Lathem, Wyndham W.; Ritzi, Marion; Knippers, Rolf; Darnell Jr., James E.
- Abstract
Stat1α is a latent cytoplasmic transcription factor activated in response to interferon-γ (IFN-γ). The C-terminal 38 amino acids of Stat1a 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 minichromosome 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 overexpression 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 Stat1a in a Ser727- and Leu724-dependent manner to play a role in optimal transcriptional activation.
- Subjects
TRANSCRIPTION factors; CYTOPLASM; INTERFERONS; AMINO acids; PROTEINS; PHOSPHORYLATION
- Publication
EMBO Journal, 1998, Vol 17, Issue 23, p6963
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/17.23.6963