The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer

Cells

卷:9

Marina Andrade-Tomaz¹  Clarissa Ribeiro Reily Rocha¹  Izadora de Souza¹  Luciana Rodrigues Gomes² 

[1] Departamento de Oncologia Clínica e Experimental, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04037-003, SP, Brazil;

[2] Laboratório de Ciclo Celular, Center of Toxins, Immune Response and Cell Signaling (CeTICS), Instituto Butantan, São Paulo 05503-001, SP, Brazil;

关键词: autophagy;    chaperone-mediated autophagy (CMA), cell cycle;    cancer;    checkpoints;    MYC;    hypoxia-inducible factor-1 subunit alpha (HIF-1α), checkpoint kinase 1 (CHK1);   

DOI  :  10.3390/cells9092140

来源: DOAJ

【 摘 要 】

The cell cycle involves a network of proteins that modulate the sequence and timing of proliferation events. Unregulated proliferation is the most fundamental hallmark of cancer; thus, changes in cell cycle control are at the heart of malignant transformation processes. Several cellular processes can interfere with the cell cycle, including autophagy, the catabolic pathway involved in degradation of intracellular constituents in lysosomes. According to the mechanism used to deliver cargo to the lysosome, autophagy can be classified as macroautophagy (MA), microautophagy (MI), or chaperone-mediated autophagy (CMA). Distinct from other autophagy types, CMA substrates are selectively recognized by a cytosolic chaperone, one-by-one, and then addressed for degradation in lysosomes. The function of MA in cell cycle control, and its influence in cancer progression, are already well-established. However, regulation of the cell cycle by CMA, in the context of tumorigenesis, has not been fully addressed. This review aims to present and debate the molecular mechanisms by which CMA can interfere in the cell cycle, in the context of cancer. Thus, cell cycle modulators, such as MYC, hypoxia-inducible factor-1 subunit alpha (HIF-1α), and checkpoint kinase 1 (CHK1), regulated by CMA activity will be discussed. Finally, the review will focus on how CMA dysfunction may impact the cell cycle, and as consequence promote tumorigenesis.

【 授权许可】

Unknown