aPKC phosphorylation of HDAC6 results in increased deacetylation activity.
The Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by in...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4393284?pdf=render |
| _version_ | 1828369899724996608 |
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| author | Yifeng Du Michael L Seibenhener Jin Yan Jianxiong Jiang Michael C Wooten |
| author_facet | Yifeng Du Michael L Seibenhener Jin Yan Jianxiong Jiang Michael C Wooten |
| author_sort | Yifeng Du |
| collection | DOAJ |
| description | The Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by interaction with various proteins including multiple kinases. Kinase mediated phosphorylation of HDAC6 can lead to either increased or reduced activity. Our previous research has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly with the zeta isoform of Protein Kinase C (PKCζ), we sought to examine if HDAC6 could be a substrate for PKCζ phosphorylation and if so, how its activity might be regulated. Our data demonstrate that HDAC6 is not only present in a protein complex with PKCζ but can also be phosphorylated by PKCζ. We also show that specific phosphorylation of HDAC6 by PKCζ increases HDAC6 deacetylase activity resulting in reduced acetylated tubulin levels. Our findings provide novel insight into the molecular mechanism by which HDAC6, PKCζ and SQSTM1/p62 function together in protein aggregate clearance. These results also highlight a new research direction which may prove fruitful for understanding the underlying cause of several neurodegenerative diseases. |
| first_indexed | 2024-04-14T06:30:43Z |
| format | Article |
| id | doaj.art-6a0972371e654e4a95b28559eff8a428 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T06:30:43Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6a0972371e654e4a95b28559eff8a4282022-12-22T02:07:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012319110.1371/journal.pone.0123191aPKC phosphorylation of HDAC6 results in increased deacetylation activity.Yifeng DuMichael L SeibenhenerJin YanJianxiong JiangMichael C WootenThe Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by interaction with various proteins including multiple kinases. Kinase mediated phosphorylation of HDAC6 can lead to either increased or reduced activity. Our previous research has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly with the zeta isoform of Protein Kinase C (PKCζ), we sought to examine if HDAC6 could be a substrate for PKCζ phosphorylation and if so, how its activity might be regulated. Our data demonstrate that HDAC6 is not only present in a protein complex with PKCζ but can also be phosphorylated by PKCζ. We also show that specific phosphorylation of HDAC6 by PKCζ increases HDAC6 deacetylase activity resulting in reduced acetylated tubulin levels. Our findings provide novel insight into the molecular mechanism by which HDAC6, PKCζ and SQSTM1/p62 function together in protein aggregate clearance. These results also highlight a new research direction which may prove fruitful for understanding the underlying cause of several neurodegenerative diseases.http://europepmc.org/articles/PMC4393284?pdf=render |
| spellingShingle | Yifeng Du Michael L Seibenhener Jin Yan Jianxiong Jiang Michael C Wooten aPKC phosphorylation of HDAC6 results in increased deacetylation activity. PLoS ONE |
| title | aPKC phosphorylation of HDAC6 results in increased deacetylation activity. |
| title_full | aPKC phosphorylation of HDAC6 results in increased deacetylation activity. |
| title_fullStr | aPKC phosphorylation of HDAC6 results in increased deacetylation activity. |
| title_full_unstemmed | aPKC phosphorylation of HDAC6 results in increased deacetylation activity. |
| title_short | aPKC phosphorylation of HDAC6 results in increased deacetylation activity. |
| title_sort | apkc phosphorylation of hdac6 results in increased deacetylation activity |
| url | http://europepmc.org/articles/PMC4393284?pdf=render |
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