Nutrient Deprivation Promotes MCL-1 Degradation in an Autophagy-Independent Manner

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N. V. Pervushin¹, V. V. Senichkin¹, A. A. Kapusta¹, A. S. Gorbunova¹, V. O. Kaminskyy², B. Zhivotovsky^1,2, and G. S. Kopeina^1,a*

¹Faculty of Basic Medicine, Lomonosov Moscow State University, 119192 Moscow, Russia

²Institute of Environmental Medicine, Karolinska Institute, 17177 Stockholm, Sweden

^* To whom correspondence should be addressed.

Received July 10, 2020; Revised August 7, 2020; Accepted August 26, 2020

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The antiapoptotic protein Mcl-1, which is an attractive target for cancer treatment, is degraded under nutrient deprivation conditions in different types of cancer. This process sensitizes cancer cells to chemotherapy. It has been found that nutrient deprivation leads to suppression of Mcl-1 synthesis; however, the mechanisms of Mcl-1 degradation under such conditions remain to be elucidated. In this study, we have investigated the contribution of autophagy and proteasomal degradation to the regulation of the level of Mcl-1 protein under nutrient deprivation conditions. We found that these circumstances cause a decrease in the level of Mcl-1 in cancer cells in a macroautophagy-independent manner via proteasomal degradation.

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KEY WORDS: apoptosis, autophagy, Mcl-1, nutrient deprivation, adenocarcinoma

DOI: 10.1134/S0006297920100119

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