Mitosin/CENP-F as a negative regulator of activating transcription factor-4.
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.
Zhou
Xubin
X
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Wang
Rong
R
Fan
Libin
L
Li
Yan
Y
Ma
Li
L
Yang
Zhenye
Z
Yu
Wei
W
Jing
Naihe
N
Zhu
Xueliang
X
D051701:Activating Transcription Factor 4; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D016350:Leucine Zippers; D046911:Macromolecular Substances; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
C497109:ATF4 protein, human; D002868:Chromosomal Proteins, Non-Histone; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C094772:centromere protein F; D051701:Activating Transcription Factor 4; D004247:DNA