The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation

Kim, Byeong Won; Jin, Yunjung; Kim, Jiyea; Kim, Jun Hoe; Jung, Juneyoung; Kang, Seongman; Kim, Ick Young; Kim, Joungmok; Cheong, Heesun; Song, Hyun Kyu

doi:10.1080/15548627.2018.1504716

Cited by 44 publications

(50 citation statements)

References 55 publications

(100 reference statements)

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“…The mammalian genome contains a total of five ATG1 homologues, ULK1, ULK2, ULK3, ULK4, and STK36 [29]. Among them, only ULK1 and ULK2 exhibit extensive sequence similarity over the entire protein length [30], whereas ULK3, ULK4, and STK36 only have sequence similarity to the Atg1 gene in the kinase structure domain [31].…”

Section: Structure Of Ulk1 and Its Biological Functions In Tumorsmentioning

confidence: 99%

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A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Liu

Liao

et al. 2020

Cancers

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The difficulty of early diagnosis and the development of drug resistance are two major barriers to the successful treatment of cancer. Autophagy plays a crucial role in several cellular functions, and its dysregulation is associated with both tumorigenesis and drug resistance. Unc-51-like kinase 1 (ULK1) is a serine/threonine kinase that participates in the initiation of autophagy. Many studies have indicated that compounds that directly or indirectly target ULK1 could be used for tumor therapy. However, reports of the therapeutic effects of these compounds have come to conflicting conclusions. In this work, we reviewed recent studies related to the effects of ULK1 on the regulation of autophagy and the development of drug resistance in cancers, with the aim of clarifying the mechanistic underpinnings of this therapeutic target.

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Section: Structure Of Ulk1 and Its Biological Functions In Tumorsmentioning

confidence: 99%

“…Table 1. Identity of ULK1 in Homo sapiens as compared with its homologues in other model organisms [28][29][30][31][32][33][34]40].…”

Section: Structure Of Ulk1 and Its Biological Functions In Tumorsmentioning

confidence: 99%

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Liu

Liao

et al. 2020

Cancers

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“…The LIR domains of ULK1 and ATG13 in humans can mediate their interaction with ATG8s [ 31 ]. The ATG13 containing HORMA domain forms a heterodimer with ATG101 containing HORMA domain [ 32 ]. Therefore, the association of ATG101 with ATG13 is the key to autophagy induction [ 33 ].…”

Section: Atg Family and Mtorc1-related Remodeling Within Invertebratementioning

confidence: 99%

Autophagy and its role in regeneration and remodeling within invertebrate

et al. 2020

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Background Acting as a cellular cleaner by packaging and transporting defective proteins and organelles to lysosomes for breakdown, autophagic process is involved in the regulation of cell remodeling after cell damage or cell death in both vertebrate and invertebrate. In human, limitations on the regenerative capacity of specific tissues and organs make it difficult to recover from diseases. Comprehensive understanding on its mechanism within invertebrate have strong potential provide helpful information for challenging these diseases. Method In this study, recent findings on the autophagy function in three invertebrates including planarian, hydra and leech with remarkable regenerative ability were summarized. Furthermore, molecular phylogenetic analyses of DjATGs and HvATGs were performed on these three invertebrates compared to that of Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens. Results In comparison with Scerevisiae, C elegans, D melanogaster, M musculus and human, our analysis exhibits the following characteristics of autophagy and its function in regeneration within invertebrate. Phylogenetical analysis of ATGs revealed that most autophagy-related genes (ATGs) were highly similar to their homologs in other species, which indicates that autophagy is a highly conservative biological function in both vertebrate and invertebrate. Structurally, almost all the core amino acids necessary for the function of ATG8 in mammal were observed in invertebrate HvATG8s and DjATG8s. For instance, ubiquitin-like domain as a signature structure in each ATG8, was observed in all ATG8s in three invertebrates. Basically, autophagy plays a key role in the regulation of regeneration in planarian. DjATG8-2 and DjATG8-3 associated with mTOR signaling pathway are sophisticated in the invertebrate tissue/organ regeneration. Furthermore, autophagy is involved in the pathway of neutralization of toxic molecules input from blood digestion in the leech. Conclusions The recent investigations on autophagy in invertebrate including planarian, hydra and leech suggest that autophagy is evolutionally conserved from yeast to mammals. The fundamental role of its biological function in the invertebrate contributing to the regeneration and maintenance of cellular homeostasis in these three organisms could make tremendous information to confront life threatening diseases in human including cancers and cardiac disorders.

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“…Other structures of the partial components of the ULK1/ATG1 complex has also been studied in the past decade, including the kinase ATG1/ULK1/2 and the ATG13-ATG101 complex. Among them, the ATG13-ATG101 is one of the complexes that has been extensively studied [34,41,43]. The ATG13-ATG101 complex in both fission yeast and mammal displays a conserved architecture with ATG13 and ATG101 in C-Mad2 and O-Mad2 conformations, respectively.…”

Section: The Ulk1/atg1 Complexmentioning

confidence: 99%

“…The WF finger of the ATG101, which is required for recruiting downstream regulators including WIPI1 and ZFYVE1, folds from an open to a closed conformation upon the binding to ATG13 [41,42]. In addition, the interaction between ATG13 and ATG101 induces the conversion of a β-strand to α-helical structure within the ATG101 C-terminal region, which further mediates the recruitment of PI3KC3 complex by direct interaction [43].…”

Section: The Ulk1/atg1 Complexmentioning

confidence: 99%

Structural Biology and Electron Microscopy of the Autophagy Molecular Machinery

Lai

Zhang

et al. 2019

Cells

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Autophagy is a highly regulated bulk degradation process that plays a key role in the maintenance of cellular homeostasis. During autophagy, a double membrane-bound compartment termed the autophagosome is formed through de novo nucleation and assembly of membrane sources to engulf unwanted cytoplasmic components and targets them to the lysosome or vacuole for degradation. Central to this process are the autophagy-related (ATG) proteins, which play a critical role in plant fitness, immunity, and environmental stress response. Over the past few years, cryo-electron microscopy (cryo-EM) and single-particle analysis has matured into a powerful and versatile technique for the structural determination of protein complexes at high resolution and has contributed greatly to our current understanding of the molecular mechanisms underlying autophagosome biogenesis. Here we describe the plant-specific ATG proteins and summarize recent structural and mechanistic studies on the protein machinery involved in autophagy initiation with an emphasis on those by single-particle analysis.

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The C-terminal region of ATG101 bridges ULK1 and PtdIns3K complex in autophagy initiation

Cited by 44 publications

References 55 publications

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Autophagy and its role in regeneration and remodeling within invertebrate

Structural Biology and Electron Microscopy of the Autophagy Molecular Machinery

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