Regulation of the Tumor-Suppressor BECLIN 1 by Distinct Ubiquitination Cascades

Boutouja, Fahd; Brinkmeier, Rebecca; Mastalski, Thomas; Magraoui, Fouzi El; Platta, Harald W.

doi:10.3390/ijms18122541

Cited by 42 publications

(38 citation statements)

References 179 publications

(248 reference statements)

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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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“…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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“…It is well documented that Beclin-1 promotes autophagy by binding to Vps34 via its conserved domain that was reported essential for tumor suppression. Recently, phosphorylation of multiple tyrosine residues of beclin1 has also been observed, which leads to a decrease in the activity of beclin1/ PI3KC3 complex and thereby the reduction of autophagy [46] .…”

Section: Autophagy Acts As a Tumor Suppressor During Tumorigenesismentioning

confidence: 99%

Targeting autophagy with small molecules for cancer therapy

Kondapuram¹,

Sarvagalla²,

Coumar³

2019

JCMT

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Autophagy is a conserved lysosomal-dependent catabolic process that maintains the cellular homeostasis by recycling misfolded proteins and damaged organelles. It involves a series of ordered events (initiation, nucleation, elongation, lysosomal fusion and degradation) that are tightly regulated/controlled by diverse cell signals and stress. It is like a double-edged sword that can play either a protective or destructive role in cancer, by pro-survival or apoptotic cues. Recently, modulating autophagy by pharmacological agents has become an attractive strategy to treat cancer. Currently, a number of small molecules that inhibit autophagy initiation (e.g., ULK kinase inhibitors), nucleation (e.g., Vps34 inhibitors), elongation (e.g., ATG4 inhibitors) and lysosome fusion (e.g., chloroquine, hydroxyl chloroquine, etc .) are reported in pre-clinical and clinical study. Also a number of small molecules reported to induce autophagy by targeting mammalian target of rapamycin (e.g., rapamycin analogs) or adenosine 5'-monophosphateactivated protein kinase (e.g., sulforaphane). The study results suggest that many potential "druggable" targets exist in the autophagy pathway that could be harnessed for developing new cancer therapeutics. In this review, we discuss the reported autophagy modulators (inhibitors and inducers), their molecular mode of action and their applications in cancer therapy.

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“…Posttranslational modifications on autophagy regulators contribute to the rapid and efficient response to various stresses. If attention is focused first on phosphorylation, a growing body of evidence shows that ubiquitination also plays a crucial role in the dynamic regulation of autophagy notably by targeting substrates to autophagosome, and modifying the activity of ULK1 and PI3K-III complexes [ 11 , 37 , 38 ].…”

Section: Autophagy and Ubiquitin System: A Brief Overviewmentioning

confidence: 99%

“…Beclin1 also interacts transiently with accessory factors, such as ATG14L, AMBRA1, UVRAG or Bcl-2 [ 65 ]. Moreover, Beclin1 versatile ubiquitination is tightly linked to its function and activation [ 37 ]. Different types of ubiquitin chains, including K63- and K48-linked chains, were found on Beclin1, and several DUBs control Beclin1 ubiquitination status and activity ( Figure 3 C).…”

Section: Deubiquitinating Enzymes Involved In Autophagymentioning

confidence: 99%

Deubiquitinating Enzymes Related to Autophagy: New Therapeutic Opportunities?

Jacomin

Taillebourg

Fauvarque

2018

Cells

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Autophagy is an evolutionary conserved catabolic process that allows for the degradation of intracellular components by lysosomes. This process can be triggered by nutrient deprivation, microbial infections or other challenges to promote cell survival under these stressed conditions. However, basal levels of autophagy are also crucial for the maintenance of proper cellular homeostasis by ensuring the selective removal of protein aggregates and dysfunctional organelles. A tight regulation of this process is essential for cellular survival and organismal health. Indeed, deregulation of autophagy is associated with a broad range of pathologies such as neuronal degeneration, inflammatory diseases, and cancer progression. Ubiquitination and deubiquitination of autophagy substrates, as well as components of the autophagic machinery, are critical regulatory mechanisms of autophagy. Here, we review the main evidence implicating deubiquitinating enzymes (DUBs) in the regulation of autophagy. We also discuss how they may constitute new therapeutic opportunities in the treatment of pathologies such as cancers, neurodegenerative diseases or infections.

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Regulation of the Tumor-Suppressor BECLIN 1 by Distinct Ubiquitination Cascades

Cited by 42 publications

References 179 publications

The Role of Beclin 1-Dependent Autophagy in Cancer

The Role of Beclin 1-Dependent Autophagy in Cancer

Targeting autophagy with small molecules for cancer therapy

Deubiquitinating Enzymes Related to Autophagy: New Therapeutic Opportunities?

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