The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Identification of a Signal-Responsive Nuclear Export Sequence in Class II Histone Deacetylases
Open accessAbstract
Activation of muscle-specific genes by the MEF2 transcription factor is inhibited by class II histone deacetylases (HDACs) 4 and 5, which contain carboxy-terminal deacetylase domains and amino-terminal extensions required for association with MEF2. The inhibitory action of HDACs is overcome by myogenic signals which disrupt MEF2-HDAC interactions and stimulate nuclear export of these transcriptional repressors. Nucleocytoplasmic trafficking of HDAC5 is mediated by binding of the chaperone protein 14-3-3 to two phosphoserine residues (Ser-259 and Ser-498) in its amino-terminal extension. Here we show that HDAC4 and -5 each contain a signal-responsive nuclear export sequence (NES) at their extreme carboxy termini. The NES is conserved in another class II HDAC, HDAC7, but is absent in class I HDACs and the HDAC-related corepressor, MEF2-interacting transcription repressor. Our results suggest that this conserved NES is inactive in unphosphorylated HDAC5, which is localized to the nucleus, and that calcium-calmodulin-dependent protein kinase (CaMK)-dependent binding of 14-3-3 to phosphoserines 259 and 498 activates the NES, with consequent export of the transcriptional repressor to the cytoplasm. A single amino acid substitution in this NES is sufficient to retain HDAC5 in the nucleus in the face of CaMK signaling. These findings provide molecular insight into the mechanism by which extracellular cues alter chromatin structure to promote muscle differentiation and other MEF2-regulated processes.
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Cites
The language of covalent histone modifications
Strahl, B. D., & Allis, C. D. (2000) · Nature · doi:10.1038/47412 · Cited by 8,679
Transport Between the Cell Nucleus and the Cytoplasm
Görlich, D., & Kutay, U. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.607 · Cited by 2,022
Control of memory formation through regulated expression of a CaMKII transgene
Mayford, M., Bach, M. E., Huang, Y.-Y., Wang, L., Hawkins, R. D., & Kandel, E. R. (1996) · Science · doi:10.1126/science.274.5293.1678 · Cited by 1,550
Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation
McKinsey, T. A., Zhang, C.-L., Lu, J., & Olson, E. N. (2000) · Nature · doi:10.1038/35040593 · Cited by 1,052
Self-citationTRANSCRIPTIONAL CONTROL OF MUSCLE DEVELOPMENT BY MYOCYTE ENHANCER FACTOR-2 (MEF2) PROTEINS
Black, B. L., & Olson, E. N. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.167 · Cited by 1,039
Self-citationThree proteins define a class of human histone deacetylases related to yeast Hda1p
Grozinger, C. M., Hassig, C. A., & Schreiber, S. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.9.4868 · Cited by 770
Grozinger, C. M., & Schreiber, S. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140199597 · Cited by 588
HDAC4 deacetylase associates with and represses the MEF2 transcription factor
Miska, E. A. (1999) · The EMBO Journal · doi:10.1093/emboj/18.18.5099 · Cited by 555
Lu, J., McKinsey, T. A., Zhang, C.-L., & Olson, E. N. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00025-3 · Cited by 547
Self-citationCaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo
Passier, R., Zeng, H., Frey, N., Naya, F. J., Nicol, R. L., McKinsey, T. A., Overbeek, P., Richardson, J. A., Grant, S. R., & Olson, E. N. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8551 · Cited by 521
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Cited by
Cardiac Hypertrophy: The Good, the Bad, and the Ugly
Frey, N., & Olson, E. N. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142243 · Cited by 1,449
Self-citationAnalysis and prediction of leucine-rich nuclear export signals
la Cour, T., Kiemer, L., Mølgaard, A., Gupta, R., Skriver, K., & Brunak, S. (2004) · Protein Engineering, Design and Selection · doi:10.1093/protein/gzh062 · Cited by 759
MEF2: a calcium-dependent regulator of cell division, differentiation and death
McKinsey, T. A., Zhang, C. L., & Olson, E. N. (2002) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)02031-x · Cited by 687
Self-citationHDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics
Gallinari, P., Marco, S. D., Jones, P., Pallaoro, M., & Steinkühler, C. (2007) · Cell Research · doi:10.1038/sj.cr.7310149 · Cited by 678
Class II histone deacetylases: versatile regulators
Verdin, E., Dequiedt, F., & Kasler, H. G. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00073-8 · Cited by 664
Metadata
- Authors
- McKinsey, T. A., Zhang, C. L., & Olson, E. N.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-09-01
- Volume
- 21
- Issue
- 18
- Pages
- 6312-6321
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2171347864
- Cited by
- 284
- References
- 39
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- green
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