British Journal of Medicine and Medical Research, ISSN: 2231-0614,Vol.: 14, Issue.: 9
The Hsp90 Chaperone Machinery: An Important Hub in Protein Interaction Networks
Jürgen Radons1* 1Scientific Consulting International, Altötting, Germany.
1Scientific Consulting International, Altötting, Germany.
(1) Crispim Cerutti Junior, Department of Social Medicine, Federal University of Espirito Santo, Brazil.
(1) Jose Gutierrez-Salinas, Institute for Social Security and Services for State Workers, Mexico.
(2) C. K. Krishnan Nair, St. Gregorios Medica Research Centre, Kerala, India.
Complete Peer review History: http://sciencedomain.org/review-history/13840
Heat shock protein 90 (Hsp90) represents one of the most conserved proteins in living organisms and is present in all kingdoms of life except for Archaea. HSP90 proteins define a widespread family of molecular chaperones that play a fundamental role in protein homoeostasis and viability. HSP90s mediate folding and maturation of a broad spectrum of client proteins including steroid hormone receptors, transcription factors, and protein kinases. HSP90s primarily exist as homodimers whose activity is regulated by ATP. Hsp90 can adopt different ATP-triggered conformations, ranging from an open V-shaped unliganded to a closed ATP-bound state. HSP90 chaperones can be found not only in the cytosol, ER, chloroplasts, mitochondria, and the nucleus but also in the extracellular milieu where they act as potent stimulators of immune responses. The activity of Hsp90 is regulated by post-translational modifications and its association with numerous co-chaperones and client proteins involved in signal transduction and transcriptional regulation. Elevated levels of HSP90s can be found in a broad spectrum of cancers where they enhance cell growth, suppress senescence, and confer resistance to stress-induced apoptosis, including protection against cytostatic drugs and radiation therapy. Since numerous oncoproteins are clients of Hsp90, targeting Hsp90 represents a useful anti-cancer approach. In this review, the current knowledge on the Hsp90 chaperone machinery and its role in disease and therapy is compiled.
Hsp90; regulation; function; therapeutic implications; disease relevance; steroid hormone receptor; inhibitors.
Full Article - PDF Page 1-32
DOI : 10.9734/BJMMR/2016/24631Review History Comments