The aggresome pathway as a target for therapy in hematologic malignancies

Tiffany Simms-Waldrip, Agustin Rodriguez-Gonzalez, Tara Lin, Alan K. Ikeda, Cecilia Fu, Kathleen M. Sakamoto

Research output: Contribution to journalReview article

52 Scopus citations

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 α-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 α-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.

Original languageEnglish (US)
Pages (from-to)283-286
Number of pages4
JournalMolecular genetics and metabolism
Volume94
Issue number3
DOIs
StatePublished - Jul 2008

Keywords

  • Aggresomes
  • Apoptosis
  • HDAC6
  • Multiple myeloma
  • Protein degradation
  • α-Tubulin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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