PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation

Abstract Uncontrolled overactivation of autophagy may lead to autophagic cell death, suppression of which is a pro-survival strategy for tumors. However, mechanisms involving key regulators in modulating autophagic cell death remain poorly defined. Here, we report a novel long noncoding RNA, p53 upr...

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Autores principales:	Shuo Han, Xue Li, Ke Wang, Dingheng Zhu, Bingyao Meng, Jieyu Liu, Xiaoting Liang, Yi Jin, Xingyuan Liu, Qian Wen, Liang Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/db4c416fb1a0469aab12a11e92571303
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spelling	oai:doaj.org-article:db4c416fb1a0469aab12a11e925713032021-11-14T12:06:53ZPURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation10.1038/s41419-021-04362-82041-4889https://doaj.org/article/db4c416fb1a0469aab12a11e925713032021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04362-8https://doaj.org/toc/2041-4889Abstract Uncontrolled overactivation of autophagy may lead to autophagic cell death, suppression of which is a pro-survival strategy for tumors. However, mechanisms involving key regulators in modulating autophagic cell death remain poorly defined. Here, we report a novel long noncoding RNA, p53 upregulated regulator of p53 levels (PURPL), functions as an oncogene to promote cell proliferation, colony formation, migration, invasiveness, and inhibits cell death in melanoma cells. Mechanistic studies showed that PURPL promoted mTOR-mediated ULK1 phosphorylation at Ser757 by physical interacting with mTOR and ULK1 to constrain autophagic response to avoid cell death. Loss of PURPL led to AMPK-mediated phosphorylation of ULK1 at Ser555 and Ser317 to over-activate autophagy and induce autophagic cell death. Our results identify PURPL as a key regulator to modulate the activity of autophagy initiation factor ULK1 to repress autophagic cell death in melanoma and may represent a potential intervention target for melanoma therapy.Shuo HanXue LiKe WangDingheng ZhuBingyao MengJieyu LiuXiaoting LiangYi JinXingyuan LiuQian WenLiang ZhouNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Shuo Han Xue Li Ke Wang Dingheng Zhu Bingyao Meng Jieyu Liu Xiaoting Liang Yi Jin Xingyuan Liu Qian Wen Liang Zhou PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation
description	Abstract Uncontrolled overactivation of autophagy may lead to autophagic cell death, suppression of which is a pro-survival strategy for tumors. However, mechanisms involving key regulators in modulating autophagic cell death remain poorly defined. Here, we report a novel long noncoding RNA, p53 upregulated regulator of p53 levels (PURPL), functions as an oncogene to promote cell proliferation, colony formation, migration, invasiveness, and inhibits cell death in melanoma cells. Mechanistic studies showed that PURPL promoted mTOR-mediated ULK1 phosphorylation at Ser757 by physical interacting with mTOR and ULK1 to constrain autophagic response to avoid cell death. Loss of PURPL led to AMPK-mediated phosphorylation of ULK1 at Ser555 and Ser317 to over-activate autophagy and induce autophagic cell death. Our results identify PURPL as a key regulator to modulate the activity of autophagy initiation factor ULK1 to repress autophagic cell death in melanoma and may represent a potential intervention target for melanoma therapy.
format	article
author	Shuo Han Xue Li Ke Wang Dingheng Zhu Bingyao Meng Jieyu Liu Xiaoting Liang Yi Jin Xingyuan Liu Qian Wen Liang Zhou
author_facet	Shuo Han Xue Li Ke Wang Dingheng Zhu Bingyao Meng Jieyu Liu Xiaoting Liang Yi Jin Xingyuan Liu Qian Wen Liang Zhou
author_sort	Shuo Han
title	PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation
title_short	PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation
title_full	PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation
title_fullStr	PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation
title_full_unstemmed	PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation
title_sort	purpl represses autophagic cell death to promote cutaneous melanoma by modulating ulk1 phosphorylation
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/db4c416fb1a0469aab12a11e92571303
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PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation

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