Chaperone‐mediated autophagy (CMA) is a catabolic pathway fundamental for cell homeostasis, by which specific damaged or non‐essential proteins are degraded. CMA activity has three main levels of regulation. The first regulatory level is based on the targetability of specific proteins possessing a KFERQ‐like domain, which can be recognized by specific chaperones and delivered to the lysosomes. Target protein unfolding and translocation into the lysosomal lumen constitutes the second level of CMA regulation and is based on the modulation of Lamp2A multimerization. Finally, the activity of some accessory proteins represents the third regulatory level of CMA activity. CMA’s role in oncology has not been fully clarified covering both pro-survival and pro‐death roles in different contexts. Taking all this into account, it is possible to comprehend the actual complexity of both CMA regulation and the cellular consequences of its activity allowing it to be elected as a modulatory and not only catabolic machinery. In this review, the role covered by CMA in oncology is discussed with a focus on its relevance in glioma. Molecular correlates of CMA importance in glioma responsiveness to treatment are described to identify new early efficacy biomarkers and new therapeutic targets to overcome resistance.

The multifaceted role of cma in glioma: Enemy or ally? / A. Lo Dico, C. Martelli, C. Diceglie, L. Ottobrini. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:4(2021 Feb 23), pp. 2217.1-2217.15. [10.3390/ijms22042217]

The multifaceted role of cma in glioma: Enemy or ally?

A. Lo Dico
Primo
;
C. Martelli
Secondo
;
C. Diceglie
Penultimo
;
L. Ottobrini
Ultimo
2021

Abstract

Chaperone‐mediated autophagy (CMA) is a catabolic pathway fundamental for cell homeostasis, by which specific damaged or non‐essential proteins are degraded. CMA activity has three main levels of regulation. The first regulatory level is based on the targetability of specific proteins possessing a KFERQ‐like domain, which can be recognized by specific chaperones and delivered to the lysosomes. Target protein unfolding and translocation into the lysosomal lumen constitutes the second level of CMA regulation and is based on the modulation of Lamp2A multimerization. Finally, the activity of some accessory proteins represents the third regulatory level of CMA activity. CMA’s role in oncology has not been fully clarified covering both pro-survival and pro‐death roles in different contexts. Taking all this into account, it is possible to comprehend the actual complexity of both CMA regulation and the cellular consequences of its activity allowing it to be elected as a modulatory and not only catabolic machinery. In this review, the role covered by CMA in oncology is discussed with a focus on its relevance in glioma. Molecular correlates of CMA importance in glioma responsiveness to treatment are described to identify new early efficacy biomarkers and new therapeutic targets to overcome resistance.
Autophagy; Chaperone proteins; Hypoxia Inducible Factor‐ 1α (HIF‐1α); Oxidative stress; PHLPP1; Temozolomide (TMZ); Therapeutic target
Settore MED/50 - Scienze Tecniche Mediche Applicate
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/825951
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