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The Role of TRAP1, the Mitochondrial Hsp90 in Cancer Progression and as a Possible Therapeutic Target


Affiliations
1 Department of Zoology, Gurudas College, 1/1 Suren Sarkar Road, Narkeldanga, Kolkata 700 054, India
 

Hsp90, a 90 kDa heat shock protein (HSP), is a molecular chaperone involved in various cellular processes. It is highly conserved across species and plays a critical role in protein folding quality control, protein degradation and, most importantly, stabilizing proteins against heat stress. Emerging evidences suggest that HSPs accumulate not only in stressful conditions, but also in patho-physiological conditions and tumours. They play a role in refolding partially damaged functional proteins and also stabilize cell survival factors. Studies also suggest the role of organelle-specific Hsp90 chaperones in these processes, which further adds to the complexity. These findings make the Hsp90 family a potent target for anti-cancer drugs. Tumour necrosis factor receptor-associated protein 1 (TRAP1), the mitochondrial homolog of Hsp90, is found to play a pivotal role in mitochondrial bioenergetics, maintenance of mitochondrial integrity and mounting stress responses. Tumour cells exhibit a peculiar phenotype known as the Warburg effect, where they evade the mitochondrial oxidative phosphorylation and produce ATP by aerobic glycolysis. Studies suggest TRAP1 as a key regulator in this metabolic switchover along with a pivotal role in drug resistance and anti-apoptotic effects. This article discusses the molecular mechanisms of TRAP1 to regulate cancer growth, its role in protecting cells from apoptosis and toxicity from anti-cancer drugs. The possibility of TRAP1 as a potential target for cancer therapies in the near future based on new-age therapeutic strategies by inhibiting the protein is also discussed here.

Keywords

Apoptosis, Cancer Progression, Drug Resistance, Heat Shock Proteins, Tumour Cells.
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  • The Role of TRAP1, the Mitochondrial Hsp90 in Cancer Progression and as a Possible Therapeutic Target

Abstract Views: 232  |  PDF Views: 132

Authors

Sena Sarkar
Department of Zoology, Gurudas College, 1/1 Suren Sarkar Road, Narkeldanga, Kolkata 700 054, India
Babli Halder
Department of Zoology, Gurudas College, 1/1 Suren Sarkar Road, Narkeldanga, Kolkata 700 054, India

Abstract


Hsp90, a 90 kDa heat shock protein (HSP), is a molecular chaperone involved in various cellular processes. It is highly conserved across species and plays a critical role in protein folding quality control, protein degradation and, most importantly, stabilizing proteins against heat stress. Emerging evidences suggest that HSPs accumulate not only in stressful conditions, but also in patho-physiological conditions and tumours. They play a role in refolding partially damaged functional proteins and also stabilize cell survival factors. Studies also suggest the role of organelle-specific Hsp90 chaperones in these processes, which further adds to the complexity. These findings make the Hsp90 family a potent target for anti-cancer drugs. Tumour necrosis factor receptor-associated protein 1 (TRAP1), the mitochondrial homolog of Hsp90, is found to play a pivotal role in mitochondrial bioenergetics, maintenance of mitochondrial integrity and mounting stress responses. Tumour cells exhibit a peculiar phenotype known as the Warburg effect, where they evade the mitochondrial oxidative phosphorylation and produce ATP by aerobic glycolysis. Studies suggest TRAP1 as a key regulator in this metabolic switchover along with a pivotal role in drug resistance and anti-apoptotic effects. This article discusses the molecular mechanisms of TRAP1 to regulate cancer growth, its role in protecting cells from apoptosis and toxicity from anti-cancer drugs. The possibility of TRAP1 as a potential target for cancer therapies in the near future based on new-age therapeutic strategies by inhibiting the protein is also discussed here.

Keywords


Apoptosis, Cancer Progression, Drug Resistance, Heat Shock Proteins, Tumour Cells.

References





DOI: https://doi.org/10.18520/cs%2Fv124%2Fi6%2F671-685