Revealing the role of epigenetic and post-translational modulations of autophagy proteins in the regulation of autophagy and cancer: a therapeutic approach

被引:2
作者
Chowdhury, Sougata Ghosh [1 ]
Karmakar, Parimal [1 ]
机构
[1] Jadavpur Univ, Dept Life Sci & Biotechnol, Kolkata 700032, India
关键词
Autophagy; Epigenetic factors; Post-translational modulation; Cancer therapy; ULK1; COMPLEX; PHOSPHORYLATION; KINASE; INITIATION; INHIBITOR; MTORC1; AMPK; MACROAUTOPHAGY; ACTIVATION; MACHINERY;
D O I
10.1007/s11033-023-08961-w
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autophagy is a process that is characterized by the destruction of redundant components and the removal of dysfunctional ones to maintain cellular homeostasis. Autophagy dysregulation has been linked to various illnesses, such as neurodegenerative disorders and cancer. The precise transcription of the genes involved in autophagy is regulated by a network of epigenetic factors. This includes histone modifications and histone-modifying enzymes. Epigenetics is a broad category of heritable, reversible changes in gene expression that do not include changes to DNA sequences, such as chromatin remodeling, histone modifications, and DNA methylation. In addition to affecting the genes that are involved in autophagy, the epigenetic machinery can also alter the signals that control this process. In cancer, autophagy plays a dual role by preventing the development of tumors on one hand and this process may suppress tumor progression. This may be the control of an oncogene that prevents autophagy while, conversely, tumor suppression may promote it. The development of new therapeutic strategies for autophagy-related disorders could be initiated by gaining a deeper understanding of its intricate regulatory framework. There is evidence showing that certain machineries and regulators of autophagy are affected by post-translational and epigenetic modifications, which can lead to alterations in the levels of autophagy and these changes can then trigger disease or affect the therapeutic efficacy of drugs. The goal of this review is to identify the regulatory pathways associated with post-translational and epigenetic modifications of different proteins in autophagy which may be the therapeutic targets shortly. 1. This review aims to determine the association between the post-translational modulation of autophagy proteins and the regulatory pathways.2. This review identifies the impact of a variety of autophagic inhibitors and epigenetic drugs on the maintenance and development of the process of autophagy thus revealing the role of these autophagic regulators in cancer therapy.
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页数:17
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共 118 条
[1]   AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth [J].
Altomare, DA ;
Wang, HQ ;
Skele, KL ;
De Rienzo, A ;
Klein-Szanto, AJ ;
Godwin, AK ;
Testa, JR .
ONCOGENE, 2004, 23 (34) :5853-5857
[2]   The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy [J].
Ardito, Fatima ;
Giuliani, Michele ;
Perrone, Donatella ;
Troiano, Giuseppe ;
Lo Muzio, Lorenzo .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2017, 40 (02) :271-280
[3]   The intricate regulation and complex functions of the Class III phosphoinositide 3-kinase Vps34 [J].
Backer, Jonathan M. .
BIOCHEMICAL JOURNAL, 2016, 473 :2251-2271
[4]   Trichostatin A activates FOXO1 and induces autophagy in osteosarcoma [J].
Bai, Yunjuan ;
Chen, Yun ;
Chen, Xiaochen ;
Jiang, Jiukun ;
Wang, Xiao ;
Wang, Liping ;
Wang, Jigang ;
Zhang, Jianbin ;
Gao, Liang .
ARCHIVES OF MEDICAL SCIENCE, 2019, 15 (01) :204-213
[5]  
Bejarano Eloy, 2010, Proc Am Thorac Soc, V7, P29, DOI 10.1513/pats.200909-102JS
[6]   p62/SQSTM1 at the interface of aging, autophagy, and disease [J].
Bitto, Alessandro ;
Lerner, Chad A. ;
Nacarelli, Timothy ;
Crowe, Elizabeth ;
Torres, Claudio ;
Sell, Christian .
AGE, 2014, 36 (03) :1123-1137
[7]   Branching via K11 and K48 Bestows Ubiquitin Chains with a Unique Interdomain Interface and Enhanced Affinity for Proteasomal Subunit Rpn1 [J].
Boughton, Andrew J. ;
Krueger, Susan ;
Fushman, David .
STRUCTURE, 2020, 28 (01) :29-+
[8]   Role of K63-linked ubiquitination in cancer [J].
Cao, Liangzi ;
Liu, Xiaofang ;
Zheng, Bowen ;
Xing, Chengzhong ;
Liu, Jingwei .
CELL DEATH DISCOVERY, 2022, 8 (01)
[9]   Autophagy and its role in gastric cancer [J].
Cao, Yijing ;
Luo, Yichen ;
Zou, Juan ;
Ouyang, Jun ;
Cai, Zhihong ;
Zeng, Xi ;
Ling, Hui ;
Zeng, Tiebing .
CLINICA CHIMICA ACTA, 2019, 489 :10-20
[10]   AMPK-Dependent Phosphorylation of GAPDH Triggers Sirt1 Activation and Is Necessary for Autophagy upon Glucose Starvation [J].
Chang, Chunmei ;
Su, Hua ;
Zhang, Danhong ;
Wang, Yusha ;
Shen, Qiuhong ;
Liu, Bo ;
Huang, Rui ;
Zhou, Tianhua ;
Peng, Chao ;
Wong, Catherine C. L. ;
Shen, Han-Ming ;
Lippincott-Schwartz, Jennifer ;
Liu, Wei .
MOLECULAR CELL, 2015, 60 (06) :930-940