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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Gene Expression Regulation, Neoplastic*; Carcinogenesis/*genetics ; Cell Cycle Checkpoints/*genetics ; Chaperone-Mediated Autophagy/*genetics ; Molecular Chaperones/*genetics ; Neoplasms/*genetics; Autophagy/genetics ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Checkpoint Kinase 1/genetics ; Checkpoint Kinase 1/metabolism ; Disease Progression ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lysosomes/metabolism ; Molecular Chaperones/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Proteolysis ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Signal Transduction

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.

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

0 (HIF1A protein, human)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (MYC protein, human)
0 (Molecular Chaperones)
0 (Proto-Oncogene Proteins c-myc)
EC 2.7.11.1 (CHEK1 protein, human)
EC 2.7.11.1 (Checkpoint Kinase 1)

Date Created: 20200925 Date Completed: 20210324 Latest Revision: 20210324

20250114

PMC7565978

10.3390/cells9092140

32971884