UNC51-like kinase 1, autophagic regulator and cancer therapeutic target
TLDR
Some properties of ULK1 which can regulate autophagy in cancer, which may shed new light on future cancer therapy strategies, utilizing ULK2 as a potential new target are summarized.Abstract:
Autophagy, the cell process of self-digestion, plays a pivotal role in maintaining energy homoeostasis and protein synthesis. When required, it causes degradation of long-lived proteins and damaged organelles, indicating that it may play a dual role in cancer, by both protecting against and promoting cell death. The autophagy-related gene (Atg) family, with more than 35 members, regulates multiple stages of the process. Serine/threonine protein kinase Atg1 in yeast, for example, can interact with other ATG gene products, functioning in autophagosome formation. One mammalian homologue of Atg1, UNC-51-like kinase 1 (ULK1) and its related complex ULK1-mAtg13-FIP200 can mediate autophagy under nutrient-deprived conditions, by protein-protein interactions and post-translational modifications. Although specific mechanisms of how ULK1 and its complex transduces upstream signals to the downstream central autophagy pathways is not fully understood, past studies have indicated that ULK1 can both suppress and promote tumour growth under different conditions. Here, we summarize some properties of ULK1 which can regulate autophagy in cancer, which may shed new light on future cancer therapy strategies, utilizing ULK1 as a potential new target.read more
Citations
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LncRNA PVT1 triggers Cyto-protective autophagy and promotes pancreatic ductal adenocarcinoma development via the miR-20a-5p/ULK1 Axis
Fengting Huang,Wenying Chen,Juanfei Peng,Yuanhua Li,Yanyan Zhuang,Zhe Zhu,Chunkui Shao,Wanling Yang,He-rui Yao,Shineng Zhang +9 more
TL;DR: The present study demonstrates that the “PVT1/miR-20a-5p/ULK1/autophagy” pathway modulates the development of pancreatic ductal adenocarcinoma and may be a novel target for developing therapeutic strategies for pancreatIC ductalAdenocARCinoma.
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Targeting autophagy-related protein kinases for potential therapeutic purpose.
TL;DR: The role of some autophagy-related kinase targets and kinase-mediated phosphorylation mechanisms in autophagic regulation is described and the small-molecule kinase inhibitors/activators of these targets are summarized, highlighting the opportunities of these new therapeutic agents.
Journal ArticleDOI
Discovery of a small molecule targeting ULK1-modulated cell death of triple negative breast cancer in vitro and in vivo.
Lan Zhang,Leilei Fu,Shouyue Zhang,Jin Zhang,Yuqian Zhao,Yaxin Zheng,Gu He,Shengyong Yang,Liang Ouyang,Bo Liu +9 more
TL;DR: In this paper, the ULK1-mATG13-FIP200-ATG101 was found to induce cell death in triple negative breast cancer (TNBC) cells.
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Autophagy and its implication in human oral diseases
Ya-Qin Tan,Jing Zhang,Gang Zhou +2 more
TL;DR: The mechanisms of autophagy are outlined, and the emerging roles of this process in oral cancer, periapical lesions, periodontal diseases, and oral candidiasis are highlighted.
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Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas
Tuhina Khan,Nicola Relitti,Margherita Brindisi,Stefania Magnano,Daniela M. Zisterer,Sandra Gemma,Stefania Butini,Giuseppe Campiani +7 more
TL;DR: An overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC is given, and a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery is provided.
References
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Journal ArticleDOI
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing
Yukiko Kabeya,Noboru Mizushima,Noboru Mizushima,Takashi Ueno,Akitsugu Yamamoto,Takayoshi Kirisako,Takayoshi Kirisako,Takeshi Noda,Takeshi Noda,Eiki Kominami,Yoshinori Ohsumi,Yoshinori Ohsumi,Tamotsu Yoshimori,Tamotsu Yoshimori +13 more
TL;DR: It is demonstrated that the rat microtubule‐associated protein 1 light chain 3 (LC3), a homologue of Apg8p essential for autophagy in yeast, is associated to the autophagosome membranes after processing.
Journal ArticleDOI
Autophagy fights disease through cellular self-digestion
TL;DR: Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health, and to play a role in cell death.
Journal ArticleDOI
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Journal ArticleDOI
TSC2 mediates cellular energy response to control cell growth and survival.
TL;DR: It is described that TSC2 is regulated by cellular energy levels and plays an essential role in the cellular energy response pathway and its phosphorylation by AMPK protect cells from energy deprivation-induced apoptosis.
Journal ArticleDOI
AMPK phosphorylation of raptor mediates a metabolic checkpoint.
Dana M. Gwinn,David B. Shackelford,Daniel F. Egan,Maria M. Mihaylova,Annabelle Mery,Debbie S. Vasquez,Benjamin E. Turk,Reuben J. Shaw +7 more
TL;DR: AMPK directly phosphorylates the mTOR binding partner raptor on two well-conserved serine residues, and this phosphorylation induces 14-3-3 binding to raptor, uncovering a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status.
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