J. Biol. Chem., Vol. 284, Issue 32, 21296-21306, August 7, 2009
Small Ubiquitin-like Modifier (SUMO) Modification of the Androgen Receptor Attenuates Polyglutamine-mediated Aggregation
J. Biol. Chem. Mukherjee et al. 284: 21296
Sarmistha Mukherjee
Current Position: Research associate in the laboratory of Dr. Dolores Lamb in the Scott Department of Urology at Baylor College of Medicine in Houston, Texas
Education: Ph.D. in Biochemistry from the Bose Institute at University of Calcutta, India
Non-scientific Interests: Cooking and traveling
When I joined the group of Dr Jorge Iñiguez-Lluhí in the Department of Pharmacology at the University of Michigan in 2004, I had a strong interest in studying SUMOylation of the androgen receptor and its effects on androgen receptor-based diseases. Covalent modification by small ubiquitin-like modifier (SUMO) proteins is an important regulatory mechanism for many proteins. I was intrigued by the fact that the androgen receptor and other proteins—such as Huntingtin, ataxin-1, tau, α-synuclein DJ-1, and PARK7 that are implicated in human protein aggregation diseases—are targets of SUMOylation. In the case of the androgen receptor, expansion of a polyglutamine tract in the amino-terminal region leads to its aggregation and is the cause of Kennedy disease. Similar mechanisms have been implicated in other age-dependent neurodegenerative disorders that are important public health problems such as Alzheimer and Parkinson disease. These similarities suggest that shared mechanisms underlie neurological dysfunction in all of these disorders, and raise the possibility that common therapeutic strategies may be effective for treating patients with these protein aggregation disorders.
Our work clearly demonstrates that SUMOylation can prevent hormone-dependent aggregation of polyglutamine-expanded androgen receptor, a critical step in the pathogenesis of Kennedy disease. This work is of fundamental importance because it indicates that pharmacologic manipulation of androgen receptor SUMOylation could be used as a therapeutic target to reduce neuronal toxicity. Understanding the role of SUMOylation may provide us with new therapeutic tools for treating patients with Kennedy disease and other more common protein aggregation neurodegenerative disorders. The details of our findings are reported in this paper.
Read Dr. Mukherjee's article on page 21296.
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