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Heat shock proteins--modulators of apoptosis in tumour cells
E M Creagh1, D Sheehan, T G Cotter
1Department of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Ireland.
Abstract:
Apoptosis is a genetically programmed, physiological method of cell destruction. A variety of genes are now recognised as positive or negative regulators of this process. Expression of inducible heat shock proteins (hsp) is known to correlate with increased resistance to apoptosis induced by a range of diverse cytotoxic agents and has been implicated in chemotherapeutic resistance of tumours and carcinogenesis. Intensive research on apoptosis over the past number of years has provided significant insights into the mechanisms and molecular events that occur during this process. The modulatory effects of hsps on apoptosis are well documented, however, the mechanisms of hsp-mediated protection against apoptosis remain to be fully defined, although several hypotheses have been proposed. Elucidation of these mechanisms should reveal novel targets for manipulating the sensitivity of leukaemic cells to therapy. This review aims to explain the currently understood process of apoptosis and the effects of hsps on this process. Several proposed mechanisms for hsp protection against apoptosis and the therapeutic implications of hsps in leukaemia are also discussed.
Insights
Heat shock proteins (hsps) confer resistance to apoptosis, a programmed cell death. Understanding how hsps protect cells could lead to new leukemia therapies.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis is a genetically programmed process of cell death crucial for physiological regulation.
- Heat shock proteins (hsps) are known to increase resistance to apoptosis induced by cytotoxic agents.
- Hsp involvement in tumor resistance and carcinogenesis highlights their clinical relevance.
Purpose of the Study:
- To review the current understanding of apoptosis.
- To elucidate the modulatory effects of heat shock proteins (hsps) on apoptosis.
- To discuss proposed mechanisms of hsp-mediated apoptosis protection and therapeutic implications in leukemia.
Main Methods:
- Literature review of apoptosis mechanisms.
- Analysis of heat shock protein (hsp) roles in cell death pathways.
- Discussion of proposed molecular mechanisms for hsp protection.
- Exploration of therapeutic strategies targeting hsps in leukemia.
Main Results:
- Heat shock proteins (hsps) are implicated in resistance to apoptosis.
- The precise mechanisms of hsp-mediated protection against apoptosis require further definition.
- Several hypotheses propose how hsps modulate apoptotic pathways.
Conclusions:
- Elucidating hsp-apoptosis mechanisms may reveal novel therapeutic targets for leukemia.
- Understanding hsp function is critical for developing more effective cancer treatments.
- Further research into hsps offers potential for overcoming chemotherapeutic resistance.