부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ymgme.2008.03.012 Byline: Tiffany Simms-Waldrip (a), Agustin Rodriguez-Gonzalez (a), Tara Lin (a), Alan K. Ikeda (a), Cecilia Fu (a), Kathleen M. Sakamoto (a)(b)(c) Keywords: Aggresomes; Protein degradation; Multiple myeloma; Apoptosis; HDAC6; [alpha]-Tubulin Abstract: Misfolded or unfolded proteins are often refolded with the help of chaperones or degraded by the 26S proteasome. An alternative fate of these proteins is the aggresome pathway. The microtubule-organizing center (MTOC) transports unfolded proteins to lysosomes and are degraded through autophagy. Histone deacetylase 6 (HDAC6) deacetylates [alpha]-tubulin, which is thought to be a component of the MTOC. Recently, two small molecule inhibitors of the aggresome pathway and HDAC6 have been described. One inhibitor, tubacin, prevents deacetylation of [alpha]-tubulin and produces accumulation of polyubiquitinated proteins and apoptosis. Tubacin acts synergistically with the proteasome inhibitor, bortezomib, to induce cytotoxicity in one type of hematologic malignancy, multiple myeloma. The other, LBH589, is a pan HDAC inhibitor and hydroxamic acid derivative that induces apoptosis of multiple myeloma cells resistant to conventional therapies. In this review, we summarize recent reports on targeting the aggresome pathway and HDAC6 in hematologic malignancies. Author Affiliation: (a) Division of Hematology-Oncology, Gwynne Hazen Cherry Memorial Laboratories, Mattel Children's Hospital UCLA, A2-412 MDCC CHS, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1752, USA (b) Department of Pathology & Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA (c) Division of Biology, California Institute of Technology, CA 91125, USA Article History: Received 14 February 2008; Revised 21 March 2008; Accepted 21 March 2008