The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

Mandell, Michael A.; Saha, Bhaskar; Thompson, Todd A.

doi:10.3389/fphar.2020.00308

Cited by 41 publications

(30 citation statements)

References 287 publications

(243 reference statements)

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“…Recently, TRIM27 has been classified as an oncoprotein. Consistent with this role, it is overexpressed in many cancers, including breast, endometrial, ovarian, lung, and colon [121]. TRIM27 association with the retromer and activates the cytoplasmic transcription factor, STAT3 [122].…”

Section: Oncogenic Roles Of Sorting Nexins and The Upsmentioning

confidence: 87%

Sorting Nexins in Protein Homeostasis

Hanley¹,

Cooper²

2020

Preprint

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Sorting nexins (SNXs) are a highly conserved membrane-associated protein family that plays a role in regulating protein homeostasis. This family of proteins is unified by their characteristic phox (PX) phosphoinositides binding domain. Along with binding to membranes, this family of SNXs also comprises a diverse array of protein-protein interaction motifs that are required for cellular sorting and protein trafficking. SNXs play a role in maintaining the integrity of the proteome which is essential for regulating multiple fundamental processes such as cell cycle progression, transcription, metabolism, and stress response. To tightly regulate these processes proteins must be expressed and degraded in the correct location and at the correct time. The cell employs several proteolysis mechanisms to ensure that proteins are selectively degraded at the appropriate spatiotemporal conditions. SNXs play a role in ubiquitin-mediated protein homeostasis at multiple levels including cargo localization, recycling, degradation, and function. In this review, we will discuss the role of SNXs in three different protein homeostasis systems: endocytosis lysosomal, the ubiquitin-proteasomal, and the autophagy-lysosomal system. The highly conserved nature of this protein family by beginning with the early research on SNXs and protein trafficking in yeast and lead into their important roles in mammalian systems. Underlying the importance of SNXs in protein homeostasis, genetic defects in SNXs have been linked with a variety of human diseases such as cancer, cardiovascular disease, neurogenerative disease, and viral infections.

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Section: Oncogenic Roles Of Sorting Nexins and The Upsmentioning

confidence: 87%

Sorting Nexins in Protein Homeostasis

Hanley¹,

Cooper²

2020

Preprint

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show abstract

“…While APOL1 and APOL3 can inhibit fission, promote autophagy and promote apoptosis, APOL2 and APOLd1 would trigger nonapoptotic autophagy that protects epithelial and endothelial cells from inflammation‐ or hypoxia‐linked cytotoxicity [149,165]. In addition, APOL3 could be involved in the recruitment of the proteasome for Parkin‐induced degradation of the outer mitochondrial membrane before phagophore interaction with PHB, since in yeast two‐hybrid screens [8], APOL3 was found to interact both with the proteasomal non‐ATPase regulatory subunit 2 (PMSD2), which directly binds to the core autophagy protein ATG16 [175], and with the ubiquitin E3 ligase tripartite motif‐containing protein 8 (TRIM8), which regulates autophagy [176,177].…”

Section: Discussionmentioning

confidence: 99%

The function of apolipoproteins L (APOLs): relevance for kidney disease, neurotransmission disorders, cancer and viral infection

Pays

2020

The FEBS Journal

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The discovery that apolipoprotein L1 (APOL1) is the trypanolytic factor of human serum raised interest about the function of APOLs, especially following the unexpected finding that in addition to their protective action against sleeping sickness, APOL1 C-terminal variants also cause kidney disease. Based on the analysis of the structure and trypanolytic activity of APOL1, it was proposed that APOLs could function as ion channels of intracellular membranes and be involved in mechanisms triggering programmed cell death. In this review, the recent finding that APOL1 and APOL3 inversely control the synthesis of phosphatidylinositol-4-phosphate (PI(4)P) by the Golgi PI(4)-kinase IIIB (PI4KB) is commented. APOL3 promotes Ca 2+-dependent activation of PI4KB, but due to their increased interaction with APOL3, APOL1 C-terminal variants can inactivate APOL3, leading to reduction of Golgi PI(4)P synthesis. The impact of APOLs on several pathological processes that depend on Golgi PI(4)P levels is discussed. I propose that through their effect on PI4KB activity, APOLs control not only actomyosin activities related to vesicular trafficking, but also the generation and elongation of autophagosomes induced by inflammation.

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“…Recently, TRIM27 has been classified as an oncoprotein. Consistent with this role, it is overexpressed in many cancers, including breast, endometrial, ovarian, lung, and colon [ 212 ]. TRIM27 associates with the retromer and activates the cytoplasmic transcription factor, STAT3 [ 133 ].…”

Section: Sorting Nexins In Diseasementioning

confidence: 99%

Sorting Nexins in Protein Homeostasis

Hanley

Cooper

2020

Cells

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Protein homeostasis is maintained by removing misfolded, damaged, or excess proteins and damaged organelles from the cell by three major pathways; the ubiquitin-proteasome system, the autophagy-lysosomal pathway, and the endo-lysosomal pathway. The requirement for ubiquitin provides a link between all three pathways. Sorting nexins are a highly conserved and diverse family of membrane-associated proteins that not only traffic proteins throughout the cells but also provide a second common thread between protein homeostasis pathways. In this review, we will discuss the connections between sorting nexins, ubiquitin, and the interconnected roles they play in maintaining protein quality control mechanisms. Underlying their importance, genetic defects in sorting nexins are linked with a variety of human diseases including neurodegenerative, cardiovascular diseases, viral infections, and cancer. This serves to emphasize the critical roles sorting nexins play in many aspects of cellular function.

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The Tripartite Nexus: Autophagy, Cancer, and Tripartite Motif-Containing Protein Family Members

Cited by 41 publications

References 287 publications

Sorting Nexins in Protein Homeostasis

Sorting Nexins in Protein Homeostasis

The function of apolipoproteins L (APOLs): relevance for kidney disease, neurotransmission disorders, cancer and viral infection

Sorting Nexins in Protein Homeostasis

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