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dc.contributor.authorObri, Arnaud
dc.contributor.authorMakinistoglu, Munevver Parla.
dc.contributor.authorZhang, Hong
dc.contributor.authorKarsenty, Gerard
dc.date2022-08-11T08:08:03.000
dc.date.accessioned2022-08-23T15:40:43Z
dc.date.available2022-08-23T15:40:43Z
dc.date.issued2014-06-23
dc.date.submitted2015-04-01
dc.identifier.citationJ Cell Biol. 2014 Jun 23;205(6):771-80. doi: 10.1083/jcb.201403138. <a href="http://dx.doi.org/10.1083/jcb.201403138">Link to article on publisher's site</a>. Epub 2014 Jun 16.
dc.identifier.issn0021-9525 (Linking)
dc.identifier.doi10.1083/jcb.201403138
dc.identifier.pmid24934156
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26466
dc.description.abstractParathyroid hormone (PTH) and the sympathetic tone promote Rankl expression in osteoblasts and osteoclast differentiation by enhancing cyclic adenosine monophosphate production through an unidentified transcription factor for PTH and through ATF4 for the sympathetic tone. How two extracellular cues using the same second messenger in the same cell elicit different transcriptional events is unknown. In this paper, we show that PTH favors Rankl expression by triggering the ubiquitination of HDAC4, a class II histone deacetylase, via Smurf2. HDAC4 degradation releases MEF2c, which transactivates the Rankl promoter. Conversely, sympathetic signaling in osteoblasts favors the accumulation of HDAC4 in the nucleus and its association with ATF4. In this context, HDAC4 increases Rankl expression. Because of its ability to differentially connect two extracellular cues to the genome of osteoblasts, HDAC4 is a critical regulator of osteoclast differentiation.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24934156&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see <a href="http://www.rupress.org/terms">http://www.rupress.org/terms</a>). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">http://creativecommons.org/licenses/by-nc-sa/3.0/</a>).</p>
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectActivating Transcription Factor 4
dc.subjectAnimals
dc.subjectCell Differentiation
dc.subjectCore Binding Factor Alpha 1 Subunit
dc.subjectGene Expression Regulation
dc.subjectHistone Deacetylases
dc.subjectMEF2 Transcription Factors
dc.subjectMice
dc.subjectModels, Biological
dc.subjectOsteoblasts
dc.subjectParathyroid Hormone
dc.subjectRANK Ligand
dc.subject*Signal Transduction
dc.subjectUbiquitin-Protein Ligases
dc.subjectUbiquitination
dc.subjectCell and Developmental Biology
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.titleHDAC4 integrates PTH and sympathetic signaling in osteoblasts
dc.typeJournal Article
dc.source.journaltitleThe Journal of cell biology
dc.source.volume205
dc.source.issue6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1150&amp;context=cellbiology_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cellbiology_pp/151
dc.identifier.contextkey6929801
refterms.dateFOA2022-08-23T15:40:43Z
html.description.abstract<p>Parathyroid hormone (PTH) and the sympathetic tone promote Rankl expression in osteoblasts and osteoclast differentiation by enhancing cyclic adenosine monophosphate production through an unidentified transcription factor for PTH and through ATF4 for the sympathetic tone. How two extracellular cues using the same second messenger in the same cell elicit different transcriptional events is unknown. In this paper, we show that PTH favors Rankl expression by triggering the ubiquitination of HDAC4, a class II histone deacetylase, via Smurf2. HDAC4 degradation releases MEF2c, which transactivates the Rankl promoter. Conversely, sympathetic signaling in osteoblasts favors the accumulation of HDAC4 in the nucleus and its association with ATF4. In this context, HDAC4 increases Rankl expression. Because of its ability to differentially connect two extracellular cues to the genome of osteoblasts, HDAC4 is a critical regulator of osteoclast differentiation.</p>
dc.identifier.submissionpathcellbiology_pp/151
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.source.pages771-80


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<p>This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see <a href="http://www.rupress.org/terms">http://www.rupress.org/terms</a>). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">http://creativecommons.org/licenses/by-nc-sa/3.0/</a>).</p>
Except where otherwise noted, this item's license is described as <p>This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see <a href="http://www.rupress.org/terms">http://www.rupress.org/terms</a>). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">http://creativecommons.org/licenses/by-nc-sa/3.0/</a>).</p>