Regulation of autophagy flux by E3 ubiquitin ligase Pirh2 in lung cancer

Autophagy is a special catabolic cellular program that is induced in response to deprivation of nutrients and energy starvation. During the execution of this program, cellular components, including aggregates, as well as damaged organelles and some proteins are encapsulated in special vesicles known...

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Veröffentlicht in:Biochemical and biophysical research communications 2021-07, Vol.563, p.119-125
Hauptverfasser: Fedorova, Olga, Gudovich, Anastasia, Daks, Alexandra, Baidyuk, Ekaterina, Shuvalov, Oleg, Petukhov, Alexey, Parfenyev, Sergey, Kizenko, Alena, Barlev, Nikolai A.
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Sprache:eng
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Zusammenfassung:Autophagy is a special catabolic cellular program that is induced in response to deprivation of nutrients and energy starvation. During the execution of this program, cellular components, including aggregates, as well as damaged organelles and some proteins are encapsulated in special vesicles known as autophagosomes and subsequently are degraded after fusion of autophagosomes with lysosomes. Importantly, at late stages of tumorigenesis cancer cells employ autophagy to sustain proliferation in unfavorable conditions, including anti-cancer drug therapy. E3 ubiquitin ligases play an important role in controlling autophagy. Here we demonstrate that the E3 ligase, a p53-induced RING-H2 protein (Pirh2), is involved in the regulation of autophagy in non-small cell lung cancer cells. Knockdown of Pirh2 decreased the expression of genes involved in all steps of autophagy. Concomitantly, Pirh2 knockdown cell lines exhibited much less of the processed form of LC3 compared to the respective cell lines with normal levels of Pirh2. These results were confirmed by the immune fluorescence microscopy using LC3 antibody and the LysoTracker dye. In agreement with the protective role of autophagy, cells with attenuated expression of Pirh2 were more sensitive to the treatment with doxorubicin. Collectively, we have uncovered a novel function of Pirh2 in the regulation of autophagy in lung cancer cells. [Display omitted] •E3 ubiquitin ligase Pirh2 is involved in the regulation of autophagy in non-small cell lung cancer cells.•Pirh2 knockdown decreases the expression of genes involved in all steps of autophagy.•Lung cancer cells with attenuated expression of Pirh2 are more sensitive to the doxorubicin treatment.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2021.05.024