2. Academic Validation
  3. PURPL represses autophagic cell death to promote cutaneous melanoma by modulating ULK1 phosphorylation

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

  • Cell Death Dis. 2021 Nov 10;12(11):1070. doi: 10.1038/s41419-021-04362-8.
Shuo Han  # 1,  Xue Li  # 1 2,  Ke Wang  # 1,  Dingheng Zhu  # 3,  Bingyao Meng 1,  Jieyu Liu 1,  Xiaoting Liang 1,  Yi Jin 1,  Xingyuan Liu 1,  Qian Wen 4,  Liang Zhou 5
Affiliations

Affiliations

  • 1 Department of Toxicology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.
  • 2 School of Clinical Medicine and Technology, Sichuan Vocational College of Health and Rehabilitation, Zigong, China.
  • 3 Dermatology Hospital, Southern Medical University, Guangzhou, China.
  • 4 Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China. wencaoxi@163.com.
  • 5 Department of Toxicology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China. zhzliang@smu.edu.cn.
  • # Contributed equally.
PMID: 34759263 DOI: 10.1038/s41419-021-04362-8
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.

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