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Cathepsins and HtrAs – Multitasking Proteases in Programmed Cell Death

  • Chapter
Proteases in Apoptosis: Pathways, Protocols and Translational Advances

Abstract

Apoptosis is a crucial process in embryonic development, adult tissue homeostasis as well as in selective clearance of unwanted or infected cells. It is an energy dependent process generally initiated by cellular damage, stress or several endogenous and extracellular stimuli. During apoptosis, activation of specific proteases results in breakdown of cellular machinery which finally culminates into characteristic morphological and biochemical changes and hence death. For many years, it was believed that caspases were the only enzymes responsible for the proteolytic cascades in apoptosis. However, accumulating evidences indicate that cell death can occur in a programmed fashion in absence of caspase activation. For example, other proteases, such as cathepsins and HtrAs (high temperature requirement protease A), are also involved in the initiation and/or execution of the apoptosis. These proteases are capable of triggering mitochondrial dysfunction with subsequent caspase activation and cellular demise. Cathepsins, a group of proteases enclosed in the lysosomes, have a major role in apoptosis by triggering the death receptor as well as mitochondria-mediated apoptotic pathways. Apart from cathepsins, HtrAs also have a potential role in mediating apoptosis. HtrA family proteins are serine proteases that are involved in important physiological processes, including maintenance of mitochondrial homeostasis, apoptosis and cell signaling. They are involved in the development and progression of several diseases such as cancer, neurodegenerative disorders and arthritis. HtrA proteins are described as potential modulators of programmed cell death and chemotherapy-induced cytotoxicity. This chapter summarizes our current knowledge on the structural and functional aspects of these proteins, with an emphasis on their potential roles in apoptosis.

Funding: A part of work on HtrA family was supported by grants from the Department of Biotechnology (DBT) [BT/PR10552/BRB/10/606/2008] and Department of Science and Technology [SERB/F/108/2012-13], Govt. of India.

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  1. Integrated Biophysics and Structural Biology Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, 410210, India

    Lalith K. Chaganti, Nitu Singh & Kakoli Bose

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  1. Lalith K. Chaganti
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  2. Nitu Singh
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  3. Kakoli Bose
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Correspondence to Kakoli Bose .

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  1. Tata Memorial Centre, Integrated Biophysics and Structural Biology Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Navi Mumbai, India

    Kakoli Bose

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Chaganti, L.K., Singh, N., Bose, K. (2015). Cathepsins and HtrAs – Multitasking Proteases in Programmed Cell Death. In: Bose, K. (eds) Proteases in Apoptosis: Pathways, Protocols and Translational Advances. Springer, Cham. https://doi.org/10.1007/978-3-319-19497-4_4

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