Cross Talk between HDAC Family Members

It is important to recognize that the 18 HDAC

members probably do not function independently. In fact, studies have presented ample evidence that several of these deacetylases might work in conjunction and regulate common biological targets and processes. For example, HDAC4 and HDAC5 can associate with HDAC3 (Grozinger et al., 1999; Fischle et al., 2002). These observations led to the hypothesis that HDAC3 might be the catalytic subunit for the HDAC4 deacetylase (Fischle et al., 2002). However, it is important to note that although endogenous HDAC3 is abundantly present in the NcoR and Smrt co-repressor complex, HDAC4 is not part of the complex (Yoon et al., 2003). Thus, it is unlikely that endogenous HDAC4 (or another class IIA HDAC) forms an exclusive complex with HDAC3 in vivo. We have found that HDAC4 and SIRT1 can also form a complex and this complex could be important in regulating MEF2 transcriptional activity (Zhao et al., 2005). As discussed, both HDAC1 and SIRT1 have been shown to promote p53 deacetylation (see above). Lastly, the cytoplasmically localized HDAC6 and SIRT2 were reported to interact, and both can function as tubulin deacetylases (North et al., 2003). Although the exact functional significance of this obvious cross-talk between HDAC family members remains to be defined, these observations clearly show that the various HDAC members can operate in coordination with one another.

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