The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Histone Deacetylase 4 Possesses Intrinsic Nuclear Import and Export Signals
Open accessAbstract
Nucleocytoplasmic trafficking of histone deacetylase 4 (HDAC4) plays an important role in regulating its function, and binding of 14-3-3 proteins is necessary for its cytoplasmic retention. Here, we report the identification of nuclear import and export sequences of HDAC4. While its N-terminal 118 residues modulate the nuclear localization, residues 244 to 279 constitute an authentic, strong nuclear localization signal. Mutational analysis of this signal revealed that three arginine-lysine clusters are necessary for its nuclear import activity. As for nuclear export, leucine-rich sequences located in the middle part of HDAC4 do not function as nuclear export signals. By contrast, a hydrophobic motif (MXXLXVXV) located at the C-terminal end serves as a nuclear export signal that is necessary for cytoplasmic retention of HDAC4. This motif is required for CRM1-mediated nuclear export of HDAC4. Furthermore, binding of 14-3-3 proteins promotes cytoplasmic localization of HDAC4 by both inhibiting its nuclear import and stimulating its nuclear export. Unlike wild-type HDAC4, a point mutant with abrogated MEF2-binding ability remains cytoplasmic upon exogenous expression of MEF2C, supporting the notion that direct MEF2 binding targets HDAC4 to the nucleus. Therefore, HDAC4 possesses intrinsic nuclear import and export signals for its dynamic nucleocytoplasmic shuttling, and association with 14-3-3 and MEF2 proteins affects such shuttling and thus directs HDAC4 to the cytoplasm and the nucleus, respectively.
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Cites
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Cited by
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MEF2: a calcium-dependent regulator of cell division, differentiation and death
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From neural development to cognition: unexpected roles for chromatin
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CLINICAL DEVELOPMENT OF HISTONE DEACETYLASE INHIBITORS AS ANTICANCER AGENTS
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Metadata
- Authors
- Wang, A. H., & Yang, X.-J.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-09-01
- Volume
- 21
- Issue
- 17
- Pages
- 5992-6005
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2105517676
- Cited by
- 183
- References
- 10
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- green
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