Role of the ubiquitin-like modifier FAT10 in protein degradation and ...

Introduction
(Cabrero et al., 2006). Interestingly, HDAC6 overexpression could be shown to
prevent HIV-1 envelope-dependent cell fusion and infection through the deacety-
lation of α-tubulin (Valenzuela-Fernandez et al., 2005). Furthermore, HDAC6
seems to be involved in osteoclast maturation through interaction with the RhoA-
effector mDia2 (Destaing et al., 2005), however, it is interesting to note that
HDAC6-deficient mice have only minor differences in bone density (Zhang et al.,
2008b). In addition, they display increased levels of α-tubulin and HSP90 acety-
lation, although lymphoid development as well as microtubule organization and
stability remain remarkably unaffected.
Recently, HDAC6 has emerged as a target of the pharmaceutical industry, al-
though whether the observed tumor-selective activity of HDAC6 inhibitors in-
deed results from its involvement in the clearance of misfolded proteins – as sug-
gested by their synergism with proteasome inhibitors (Hideshima et al., 2005) –
remains unclear. Especially as HDAC6 has also been implicated in tumor cell
invasion and metastasis through interaction with BRMS1 (breast cancer metas-
tasis suppressor 1, Hurst et al., 2006) and HSP90 deacetylation (Bali et al., 2005;
Fiskus et al., 2007), or its involvement in Akt-PP1 (protein phosphatase 1) medi-
ated signaling (Brush et al., 2004; Chen et al., 2005; Park et al., 2008).
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