Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling

Cheng, Minzhang; Xue, Hua; Cao, Weipeng; Li, Wenxia; Hua, Cunqing; Liu, Bofeng; Ma, Benyu; Yan, Xiaohua; Chen, Ye-Guang

doi:10.1074/jbc.m115.708818

Cited by 25 publications

(12 citation statements)

References 42 publications

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“…For a group of LIR-containing proteins, two or more LIR motifs have been found to interact with LC3B and validated by experimental mutagenesis, i.e., TER ATPase (also named VCP), PML, RACK1, Spred-2 and CRY1 (He et al, 2014;Cheng M. et al, 2016;Guo et al, 2016;Jiang et al, 2016;Toledo et al, 2018). In the cases of PML and RACK1, the C-terminal motifs seem to play the most important role in the interaction (He et al, 2014;Cheng M. et al, 2016). A secondary LIR has also been reported in PCM1 for the interaction with GABARAP, which is likely to account for the remaining binding activity when the most important LIR is mutated (Joachim et al, 2017).…”

Section: Proteins With Multiple Lirsmentioning

confidence: 99%

Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques

Sora

Kumar

Maiani

et al. 2020

Front. Cell Dev. Biol.

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Autophagy is a conserved and essential intracellular mechanism for the removal of damaged components. Since autophagy deregulation is linked to different kinds of pathologies, it is fundamental to gain knowledge on the fine molecular and structural details related to the core proteins of the autophagy machinery. Among these, the family of human ATG8 proteins plays a central role in recruiting other proteins to the different membrane structures involved in the autophagic pathway. Several experimental structures are available for the members of the ATG8 family alone or in complex with their different biological partners, including disordered regions of proteins containing a short linear motif called LC3 interacting motif. Recently, the first structural details of the interaction of ATG8 proteins with biological membranes came into light. The availability of structural data for human ATG8 proteins has been paving the way for studies on their structure-function-dynamic relationship using biomolecular simulations. Experimental and computational structural biology can help to address several outstanding questions on the mechanism of human ATG8 proteins, including their specificity toward different interactors, their association with membranes, the heterogeneity of their conformational ensemble, and their regulation by post-translational modifications. We here summarize the main results collected so far and discuss the future perspectives within the field and the knowledge gaps. Our review can serve as a roadmap for future structural and dynamics studies of the ATG8 family members in health and disease.

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Section: Proteins With Multiple Lirsmentioning

confidence: 99%

Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques

Sora

Kumar

Maiani

et al. 2020

Front. Cell Dev. Biol.

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“…Dishevelled (Dvl) is a basic and central component of WNT signaling that plays an important role in both β-catenin–mediated canonical and β-catenin–independent noncanonical WNT signaling [94]. Dvl expression and stability are negatively controlled by autophagy in the late stages of cancer development, which in turn inhibits the WNT process [95, 96]. In a further study, the WNT signaling antagonist Dapper1 was induced by autophagy-accelerated Dvl2 degradation [97], which is mediated by GABA(A) receptor–associated protein like 1 (GABARAPL1), a cancer repressor, and p62 is required for the interaction of Dvl2 and GABARAPL1.…”

Section: Crosstalk Between Autophagy and Emtmentioning

confidence: 99%

Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy

et al. 2019

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Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a “double-edged sword” in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.

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“…The literature has demonstrated the importance of autophagy in embryogenesis and development, as deletion of autophagy genes in mice leads to lethality (embryonic and neonatal stages) and defects in neuronal differentiation (26, 27). Several studies have shown the interplay between autophagy/autophagy-related genes (ATGs) and developmental pathways (Wnt, Notch, Shh, FGF, and TGF-β) in different cell models (28–33). Autophagy balances the levels of various development-related signaling proteins.…”

Section: Resultsmentioning

confidence: 99%

Quantitative Proteome Analysis of Atg5 -Deficient Mouse Embryonic Fibroblasts Reveals the Range of the Autophagy-Modulated Basal Cellular Proteome

Sharma

Aggarwal

et al. 2019

mSystems

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Autophagy performs housekeeping functions for cells and maintains a functional mode by degrading damaged proteins and organelles and providing energy under starvation conditions. The process is tightly regulated by the evolutionarily conserved Atg genes, of which Atg5 is one such crucial mediator. Here, we have done a comprehensive quantitative proteome analysis of mouse embryonic fibroblasts that lack a functional autophagy pathway (Atg5 knockout). We observe that 14% of the identified cellular proteome is remodeled, and several proteins distributed across diverse cellular processes with functions in signaling, cell adhesion, development, and immunity show either higher or lower levels under autophagy-deficient conditions. These cells have lower levels of crucial immune proteins that are required to mount a protective inflammatory response. This study will serve as a valuable resource to determine the role of autophagy in modulating specific protein levels in cells.

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Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling

Cited by 25 publications

References 42 publications

Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques

Structure and Dynamics in the ATG8 Family From Experimental to Computational Techniques

Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy

Quantitative Proteome Analysis of Atg5 -Deficient Mouse Embryonic Fibroblasts Reveals the Range of the Autophagy-Modulated Basal Cellular Proteome

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