Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO

Reidick, Christina; Magraoui, Fouzi El; Meyer, Helmut E.; Stenmark, Harald; Platta, Harald W.

doi:10.3390/cancers7010001

Cited by 27 publications

(22 citation statements)

References 189 publications

(272 reference statements)

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“…In the cytosol, UPS and AL pathways act simultaneously, share components of their molecular machineries, and constantly influence each other's activity (3)(4)(5). Multiple reports indicate the autophagy receptor p62/sequestosome-1 as the principal molecule that regulates the cross-talk between the two systems (3,6,7); however, the strongest commonality between the two degradative systems is the small globular protein ubiquitin (Ub).…”

Section: Ubiquitination Is a Widespread Post-translational Modificatimentioning

confidence: 99%

Ubiquitin signaling and autophagy

Grumati

Đikić

2018

Journal of Biological Chemistry

252

189

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Ubiquitination is a widespread post-translational modification that controls multiple steps in autophagy, a major lysosome-mediated intracellular degradation pathway. A variety of ubiquitin chains are attached as selective labels on protein aggregates and dysfunctional organelles, thus promoting their autophagy-dependent degradation. Moreover, ubiquitin modification of autophagy regulatory components is essential to positively or negatively regulate autophagy flux in both non-selective and selective pathways. We review the current findings that elucidate the components, timing, and kinetics of the multivalent role of ubiquitin signals in control of amplitude and selectivity of autophagy pathways as well as their impact on the development of human diseases.

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Section: Ubiquitination Is a Widespread Post-translational Modificatimentioning

confidence: 99%

Ubiquitin signaling and autophagy

Grumati

Đikić

2018

Journal of Biological Chemistry

252

189

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“…Ubiquitination is also an important post-translational modification regulating Beclin 1, and there are excellent and extensive reviews available that address it [79,80].…”

Section: Other Beclin 1 Modifiersmentioning

confidence: 99%

The Role of Beclin 1-Dependent Autophagy in Cancer

Vega-Rubín-de-Celis

2019

Biology

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Autophagy (self-eating) is an intracellular degradation process used by cells to keep a "clean house"; as it degrades abnormal or damaged proteins and organelles, it helps to fight infections and also provides energy in times of fasting or exercising. Autophagy also plays a role in cancer, although its precise function in each cancer type is still obscure, and whether autophagy plays a protecting (through the clearing of damaged organelles and protein aggregates and preventing DNA damage) or a promoting (by fueling the already stablished tumor) role in cancer remains to be fully characterized. Beclin 1, the mammalian ortholog of yeast Atg6/Vps30, is an essential autophagy protein and has been shown to play a role in tumor suppression. Here, an update of the tumorigenesis regulation by Beclin 1-dependent autophagy is provided.

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“…135 There are also different circumstances that result in the linkage of BECN1 to diverse types of ubiquitin chains, which exert distinct effects on BECN1 and autophagic activity. 136,137 For instance, ubiquitination of BECN1 through Lys-11-linked 138 or Lys-48-linked 139 ubiquitin chains promotes the degradation of BECN1, which possibly decreases autophagy, whereas Lys-63-linked ubiquitination enhances autophagy through dissociating BECN1 from BCL2. 140 More importantly, BECN1 serves as a platform to coordinate various regulators of autophagy, which has been termed the "BECN1 interactome."…”

Section: Regulation Of Autophagy By Pik3c3 Via Becn1mentioning

confidence: 99%

Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy

2015

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Abbreviations: 3-MA, 3-methyladenine; AMBRA1, autophagy/Beclin 1 regulator 1; ATG, autophagy related; ATM, ATM serine/threonine kinase; ATR, ATR serine/threonine kinase; BH3, Bcl-2 homology 3; CCD, coiled-coil domain; CDK, cyclin-dependent kinase; CISD2, CDGSH iron sulfur domain 2; class I/II PI3K, class I/II phosphoinositide 3-kinase; class III PtdIns3K, class III phosphatidylinositol 3-kinase; DAPK1, death-associated protein kinase 1; DDR, DNA damage response; EIF4EBP1, eukaryotic translation initiation factor 4E binding protein 1; ER, endoplasmic reticulum; FOXO, forkhead box O; FYCO1, FYVE and coiledcoil domain containing 1; GAP, GTPase-activating protein; HMGB1, high mobility group box 1; HSPA1A, heat shock 70kDa protein 1A; IR, ionizing radiation; MAPK8, mitogen-activated protein kinase 8; MEFs, mouse embryonic fibroblasts; MTMR, myotubularin-related protein; MTOR, mechanistic target of rapamycin (serine/threonine kinase); MTORC1, mechanistic target of rapamycin complex 1; MVBs, spherical multivesicular bodies; NRBF2, nuclear receptor binding factor 2; PAS, phagophore assembly site; PDPK1, 3-phosphoinositide dependent protein kinase 1; PE, phosphatidylethanolamine; PIKFYVE, phosphoinositide kinase, FYVE finger containing; PINK1, PTEN-induced putative kinase 1; PtdIns3K-C1, class III phosphatidylinositol 3-kinase complex I; PtdIns3K-C2, class III phosphatidylinositol 3-kinase complex II; PKB, protein kinase B; PRKA, protein kinase, AMP-activated; PRKD1, protein kinase D1; PRKDC, protein kinase, DNA-activated, catalytic polypeptide; PtdIns5P, phosphatidylinositol 5-phosphate; PtdIns4P, phosphatidylinositol 4-phosphate; PtdIns(4,5)P 2 , phosphatidylinositol 4,5-bisphosphate; PtdIns3P, phosphatidylinositol 3-phosphate; PtdIns(3,5)P 2 , phosphatidylinositol 3,5-bisphosphate; PtdIns(3,4,5)P 3 , phosphatidylinositol 3,4,5-trisphosphate; RHEB, Ras homolog enriched in brain; RPS6KB1, ribosomal protein S6 kinase, 70kDa, polypeptide 1; SQSTM1, sequestosome 1; TECPR1, tectonin b-propeller repeat containing 1; TFEB, transcription factor EB; TRIM28, tripartite motif containing 28; TSC, tuberous sclerosis; UV, ultraviolet; UVRAG, UV radiation resistance associated; WDFY3, WD repeat and FYVE domain containing 3; WIPI, WD repeat domain, phosphoinositide interacting; ZFYVE1, zinc finger, FYVE domain containing 1.Autophagy is an evolutionarily conserved and exquisitely regulated self-eating cellular process with important biological functions. Phosphatidylinositol 3-kinases (PtdIns3Ks) and phosphoinositide 3-kinases (PI3Ks) are involved in the autophagic process. Here we aim to recapitulate how 3 classes of these lipid kinases differentially regulate autophagy. Generally, activation of the class I PI3K suppresses autophagy, via the well-established PI3K-AKT-MTOR (mechanistic target of rapamycin) complex 1 (MTORC1) pathway. In contrast, the class III PtdIns3K catalytic subunit PIK3C3/Vps34 forms a protein complex with BECN1 and PIK3R4 and produces phosphatidylinositol 3-phosphate (PtdIns3P), which is required for the initiati...

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Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO

Cited by 27 publications

References 189 publications

Ubiquitin signaling and autophagy

Ubiquitin signaling and autophagy

The Role of Beclin 1-Dependent Autophagy in Cancer

Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy

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