Role of the aggresome pathway in cancer: targeting histone deacetylase 6-dependent protein degradation.
Misfolded or aggregated proteins have two fates: they are either refolded with the help of chaperones or degraded by the proteasome. Cells also have an alternative pathway that involves intracellular "storage bins" for misfolded intracellular proteins known as aggresomes. Aggresomes recruit motor proteins that transport misfolded or aggregated proteins to chaperones and proteasomes for subsequent destruction. There is emerging evidence that inhibiting the aggresome pathway leads to accumulation of misfolded proteins and apoptosis in tumor cells through autophagy. We discuss the role of aggresomes in cancer and the potential to target this pathway for therapy.
Rodriguez-Gonzalez
Agustin
A
Division of Hematology-Oncology, Mattel Children's Hospital, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1752, USA.
Lin
Tara
T
Ikeda
Alan K
AK
Simms-Waldrip
Tiffany
T
Fu
Cecilia
C
Sakamoto
Kathleen M
KM
D001343:Autophagy; D002449:Cell Aggregation; D002465:Cell Movement; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D025801:Ubiquitin / Q000378:metabolism
D018832:Molecular Chaperones; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases