Abstract：
:Histone deacetylase 6 (HDAC6) is a tubulin-specific deacetylase that regulates microtubule-dependent cell movement. In this study, we identify the F-actin-binding protein cortactin as a HDAC6 substrate. We demonstrate that HDAC6 binds cortactin and that overexpression of HDAC6 leads to hypoacetylation of cortactin, whereas inhibition of HDAC6 activity leads to cortactin hyperacetylation. HDAC6 alters the ability of cortactin to bind F-actin by modulating a "charge patch" in its repeat region. Introduction of charge-preserving or charge-neutralizing mutations in this cortactin repeat region correlates with the gain or loss of F-actin binding ability, respectively. Cells expressing a charge-neutralizing cortactin mutant were less motile than control cells or cells expressing a charge-preserving mutant. These findings suggest that, in addition to its role in microtubule-dependent cell motility, HDAC6 influences actin-dependent cell motility by altering the acetylation status of cortactin, which, in turn, changes the F-actin binding activity of cortactin.
journal_name
Mol Celljournal_title
Molecular cellauthors
Zhang X,Yuan Z,Zhang Y,Yong S,Salas-Burgos A,Koomen J,Olashaw N,Parsons JT,Yang XJ,Dent SR,Yao TP,Lane WS,Seto Edoi
10.1016/j.molcel.2007.05.033subject
Has Abstractpub_date
2007-07-20 00:00:00pages
197-213issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(07)00357-7journal_volume
27pub_type
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