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Role of Proteases in Cellular Dysfunction pp 159–186Cite as

Ubiquitin–Proteasome System in the Hallmarks of Cancer

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Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 8))

Abstract

The paramount role of ubiquitin–protein conjugation for its ability to regulate protein turnover and nonproteolytic signaling functions has been implicated in the regulation of various biological and pathological phenomena. Malignant cells utilize modified ubiquitination to augment or attenuate signaling pathways on the basis of whether the outcome of this signaling is conducive or not for tumor growth and survival. Hence, there lies a necessity for a fresh view at the ubiquitin-dependent mechanisms that play an important role in human oncological diseases. To control ubiquitination-dependent mechanisms of cell transformation within tumor cells themselves, along with increased rate of protein synthesis, translation and protein quality control processes are often required to support the transforming events for their contribution to the mechanisms of tumor progression. Given that ubiquitin metabolism is governed by enzymes—E1, E2, E3, E4, deubiquitinases (DUBs), and the proteasome—the system as a whole is ripe for target and drug discovery in cancer. Recently, the hallmarks of cancer designated by Hanahan and Weinberg in 2011 comprise ten biological capabilities acquired during the multistep development of tumor. Based on these hallmarks, the present review enlightened the role of ubiquitination in every hallmark for rationalizing the complexities of neoplastic disease and also discusses therapeutic implications targeting the ubiquitin–proteasome system as well as synthetic and natural compounds with potent inhibitory effects.

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Acknowledgment

This work was supported by research grants from DST and DBT, Govt. of India.

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  1. Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII-M, Kolkata, 700054, West Bengal, India

    Pushpak Bhattacharjee, Minakshi Mazumdar, Deblina Guha & Gaurisankar Sa

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  2. Minakshi Mazumdar
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  3. Deblina Guha
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  4. Gaurisankar Sa
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Correspondence to Gaurisankar Sa .

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Editors and Affiliations

  1. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

  2. Dept of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

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© 2014 Springer Science+Business Media New York

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Bhattacharjee, P., Mazumdar, M., Guha, D., Sa, G. (2014). Ubiquitin–Proteasome System in the Hallmarks of Cancer. In: Dhalla, N., Chakraborti, S. (eds) Role of Proteases in Cellular Dysfunction. Advances in Biochemistry in Health and Disease, vol 8. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9099-9_9

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