p62 degradation by autophagy: another way for cancer cells to survive under hypoxia.
Hypoxia is a common feature of advanced solid tumors causing cancer progression and resistance to treatment. Hypoxia activates mitophagy as well as macroautophagy that regulates carcinoma cell survival. p62/SQSTM1, a multifunctional protein that targets proteins to degradation by proteasomes and autophagy, is itself downregulated by hypoxia-activated autophagy in carcinoma cells. The hypoxic degradation of p62 is seen across several carcinoma cell lines. In contrast to hypoxic activation of mitochondrial autophagy, the hypoxia-induced degradation of p62 occurs partially independently from the HIF pathway. The finding argues that in addition to transcriptional gene regulation through HIF, autophagy has a central role in the regulation of hypoxic cancer cell survival responses.
Jaakkola
Panu M
PM
Turku Centre for Biotechnology, Turku University and Abo Akademi University, Tykistökatu 6B, Turku, Finland. panjaa@utu.fi
Pursiheimo
Juha-Pekka
JP
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010766:Phosphorylation; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D048049:Extracellular Signal-Regulated MAP Kinases