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Publication : Mitosin/CENP-F as a negative regulator of activating transcription factor-4.

First Author  Zhou X Year  2005
Journal  J Biol Chem Volume  280
Issue  14 Pages  13973-7
PubMed ID  15677469 Mgi Jnum  J:125622
Mgi Id  MGI:3759337 Doi  10.1074/jbc.M414310200
Citation  Zhou X, et al. (2005) Mitosin/CENP-F as a negative regulator of activating transcription factor-4. J Biol Chem 280(14):13973-7
abstractText  Mitosin/CENP-F is a human nuclear matrix protein with multiple leucine zipper motifs. Its accumulation in S-G2 phases and transient kinetochore localization in mitosis suggest a multifunctional protein for cell proliferation. Moreover, its murine and avian orthologs are implicated in myocyte differentiation. Here we report its interaction with activating transcription factor-4 (ATF4), a ubiquitous basic leucine zipper transcription factor important for proliferation, differentiation, and stress response. The C-terminal portion of mitosin between residues 2488 and 3113 bound to ATF4 through two distinct domains, one of which was a leucine zipper motif. Mitosin mutants containing these domains were able to either supershift or disrupt the ATF4-DNA complex. On the other hand, ATF4, but not ATF1-3 or ATF6, interacted with mitosin through a region containing the basic leucine zipper motif. Moreover, overexpression of full-length mitosin repressed the transactivation activity of ATF4 in dual luciferase-based reporter assays, while knocking down mitosin expression manifested the opposite effects. These findings suggest mitosin to be a negative regulator of ATF4 in interphase through direct interaction.
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