"HSPB1 and HSPB5 as targets for treating chemoresistance in cancers"
The small heat shock proteins alpha b-crystallin (HSPB5) and heat shock protein-27kDa (HSPB1) are ubiquitously expressed molecular chaperones that protect cells from stress. Both proteins are abundant in several cancer types and are reliable indicators of poor prognosis. Overexpression of either HSPB1 or HSPB5 confers resistance to chemotherapy by inhibiting intrinsic apoptosis. Although targeted gene knockdown reduces chemoresistance in animals, protein-targeted approaches are limited by the absence of direct binding and structural data on these interactions.
This proposal aims to resolve these details through structural and biochemical studies, using a complementary cell biology approach to determine their biological significance.