Myogenic repressor I-mfa interferes with the function of Zic family proteins

Mizugishi, Kiyomi; Hatayama, Minoru; Tohmonda, Takahide; Ogawa, Miyuki; Inoue, Takashi; Mikoshiba, Katsuhiko; Aruga, Jun

doi:10.1016/j.bbrc.2004.05.158

Cited by 42 publications

(34 citation statements)

References 21 publications

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“…Previous studies have suggested that interactions involving HIC or I-mfa result in the inhibition of the activities of their partner proteins in a similar fashion, either by preventing nuclear localization or DNA binding or both (18,20,30). This is directly supported by our subcellular colocalization studies where it could be shown at a single-cell level that although Tat was predominantly nuclear when expressed on its own, coexpression of HIC and Tat resulted in a distinctive localization of Tat in the cytoplasm.…”

Section: Discussionsupporting

confidence: 86%

Direct interaction of the human I-mfa domain-containing protein, HIC, with HIV-1 Tat results in cytoplasmic sequestration and control of Tat activity

Gautier

Sheehy

Duffy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The primary function of the HIV-1 regulatory protein Tat, activation of transcription from the viral LTR, is highly regulated by complex interactions between Tat and a number of host cell proteins. Tat nuclear import, a process mediated by importin β, is a prerequisite for its activity. Here, we report and characterize the interaction of the human inhibitor of MyoD family domain-containing protein (I-mfa), HIC, with Tat at a biochemical and a functional level. This interaction was shown to occur in vivo and in vitro and to involve the nuclear localization signal and the transactivation responsive element-binding domains of Tat and the I-mfa domain of HIC. Coexpression of HIC and Tat resulted in the down-regulation of transactivation of the HIV-1 LTR, and colocalization studies revealed the cytoplasmic sequestration of Tat by HIC. Functionally this sequestration appears to be the underlying mechanism of LTR transcriptional repression by HIC and represents a unique mechanism for the control of Tat activity and regulation of HIV-1 replication.

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Section: Discussionsupporting

confidence: 86%

Direct interaction of the human I-mfa domain-containing protein, HIC, with HIV-1 Tat results in cytoplasmic sequestration and control of Tat activity

Gautier

Sheehy

Duffy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…The I-mfa protein is known to repress myogenesis by binding to and masking the nuclear localization signals of MyoD family members in mouse (Chen et al, 1996). I-mfa similarly causes the retention of Zic proteins in the cytoplasm, although it does not mask the nuclear localization signal (Mizugishi et al, 2004). Instead, I-mfa may provide a cytoplasmic anchoring site for Zic1-3 proteins.…”

Section: Interacting Proteinsmentioning

confidence: 98%

“…Thus, the N-and C-terminal domains of Zic proteins are likely to play important roles in governing Zic protein activities. A yeast two-hybrid screen identified Imfa as a protein that binds to the Ntermini of murine Zic1-3, thereby inhibiting the ability of Zic1-3 to activate transcription in cell-based reporter assays (Mizugishi et al, 2004). The I-mfa protein is known to repress myogenesis by binding to and masking the nuclear localization signals of MyoD family members in mouse (Chen et al, 1996).…”

Section: Interacting Proteinsmentioning

confidence: 99%

Emerging roles for zic genes in early development

Merzdorf

2007

Developmental Dynamics

134

126

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“…1A,B). The primary structure of Xenopus Zic4 was more similar to Oryzias latipes Zic4 (OlZic4) than to mammalian Zic4s: The N-terminal regions of human and mouse Zic4 are relatively short and lack sequences related to ZOC, an evolutionarily conserved transcription regulatory domain present in mouse Zic1, Zic2, and Zic3 (Aruga et al, 1996a;Mizugishi et al, 2004). Zic4 had the longest N-terminal region among Xenopus laevis Zic proteins (Fig.…”

Section: Structure Of Xenopus Zic4mentioning

confidence: 98%

Xenopus Zic4: Conservation and diversification of expression profiles and protein function among the Xenopus Zic family

Fujimi

Mikoshiba

Aruga

2006

Developmental Dynamics

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We compared the expression and function of Xenopus Zic4 with those of the other four Xenopus laevis Zic family members (Zic1, Zic2, Zic3, and Zic5). Zic4 expression was detected mainly in the neural plate border, dorsal neural tube, and somites, and was similar to that of Zic1, which is adjacent to Zic4 on the same chromosome. Injection of wild-type or mutant Zic4 RNA caused the induction of neural crest marker gene expression, hyperplastic neural tissue, and ectopic pigment cell formation, indicating that Zic4 can induce neural and neural crest tissue, as can other Xenopus Zic genes. Deletion analysis showed that the zinc-finger domain is critical for many Zic4 functions, but the C-terminal region is differently involved in induction of two neural crest markers, Slug and Sox10. The protein function as determined by the animal cap explant assay was similar to that of Zic5, but different from those of Zic1, Zic2, and Zic3, suggesting that Xenopus Zic genes can be divided into two groups based on function. These results indicate that the five Xenopus Zic genes cooperatively regulate both neural and neural crest development, despite significantly diverged expression profiles and functions. Developmental Dynamics 235:3379 -3386, 2006.

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Myogenic repressor I-mfa interferes with the function of Zic family proteins

Cited by 42 publications

References 21 publications

Direct interaction of the human I-mfa domain-containing protein, HIC, with HIV-1 Tat results in cytoplasmic sequestration and control of Tat activity

Direct interaction of the human I-mfa domain-containing protein, HIC, with HIV-1 Tat results in cytoplasmic sequestration and control of Tat activity

Emerging roles for zic genes in early development

Xenopus Zic4: Conservation and diversification of expression profiles and protein function among the Xenopus Zic family

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