ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

Caballe, Anna; Wenzel, Dawn M; Agromayor, Monica; Alam, Steven L.; Skalicky, Jack J.; Kloc, Magdalena; Carlton, Jeremy G.; Labrador, Leticia; Sundquist, Wesley I.; Martín-Serrano, Juan

doi:10.7554/elife.06547

Cited by 85 publications

(142 citation statements)

References 64 publications

Supporting

Mentioning

139

Contrasting

Order By: Relevance

“…The molecular mechanisms underlying the timing of asymmetric abscission in epithelial cells are thought to be complex and include an abscission checkpoint that is still not well understood (Caballe et al, 2015; Lafaurie-Janvore et al, 2013). We did not observe a defect in the ploidy of the cells, which makes a disruption of the furrow regression rather unlikely.…”

Section: Discussionmentioning

confidence: 99%

“…We did not observe a defect in the ploidy of the cells, which makes a disruption of the furrow regression rather unlikely. One possible scenario is that PRL-3 could be acting downstream of Aurora kinase B, causing a failure in abscission delay – for example, by counteracting Unc-51-like kinase 3, which is needed for the final stages of abscission (Caballe et al, 2015). In general, the knowledge of the roles and involvement of particular phosphatases in cytokinesis is very limited (Caballe et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…One possible scenario is that PRL-3 could be acting downstream of Aurora kinase B, causing a failure in abscission delay – for example, by counteracting Unc-51-like kinase 3, which is needed for the final stages of abscission (Caballe et al, 2015). In general, the knowledge of the roles and involvement of particular phosphatases in cytokinesis is very limited (Caballe et al, 2015). However, although PRL-3 localizes to the site of cytokinesis, it is unclear if its involvement is direct or indirect given that PRL-3 expression in cells affects a plethora of pathways (Rios et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position

Luján

Varsano

Rubio

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Disruption of epithelial architecture is a fundamental event during epithelial tumorigenesis. We show that the expression of the cancer-promoting phosphatase PRL-3 (PTP4A3), which is overexpressed in several epithelial cancers, in polarized epithelial MDCK and Caco2 cells leads to invasion and the formation of multiple ectopic, fully polarized lumens in cysts. Both processes disrupt epithelial architecture and are hallmarks of cancer. The pathological relevance of these findings is supported by the knockdown of endogenous PRL-3 in MCF-7 breast cancer cells grown in three-dimensional branched structures, showing the rescue from multiple-lumen- to single-lumen-containing branch ends. Mechanistically, it has been previously shown that ectopic lumens can arise from midbodies that have been mislocalized through the loss of mitotic spindle orientation or through the loss of asymmetric abscission. Here, we show that PRL-3 triggers ectopic lumen formation through midbody mispositioning without altering the spindle orientation or asymmetric abscission, instead, PRL-3 accelerates cytokinesis, suggesting that this process is an alternative new mechanism for ectopic lumen formation in MDCK cysts. The disruption of epithelial architecture by PRL-3 revealed here is a newly recognized mechanism for PRL-3-promoted cancer progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position

Luján

Varsano

Rubio

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…In addition, an autophagy-independent function for unc-51-like autophagy-activating kinase 3 (ULK3) as an abscission regulator has been reported (134). Abscission is mediated by the endosomal sorting complexes required for transport (ESCRT) machinery, which mediates membrane remodeling in a number of processes including cytokinesis, viral budding, and autophagy (135).…”

Section: Cell Division and Autophagymentioning

confidence: 99%

“…The timing of abscission is regulated by the abscission checkpoint, which delays abscission in response to a number of mitotic abnormalities (136). Interestingly, ULK3 was shown to function in the abscission checkpoint to delay abscission by phosphorylating and binding ESCRT-III subunits in response to lagging chromosomes, nuclear pore defects, and tension forces at the midbody (134). Thus, ULK3 appears to function as an integral part of the abscission checkpoint machinery.…”

Section: Cell Division and Autophagymentioning

confidence: 99%

Autophagy and the Cell Cycle: A Complex Landscape

2017

View full text Add to dashboard Cite

Autophagy is a self-degradation pathway, in which cytoplasmic material is sequestered in double-membrane vesicles and delivered to the lysosome for degradation. Under basal conditions, autophagy plays a homeostatic function. However, in response to various stresses, the pathway can be further induced to mediate cytoprotection. Defective autophagy has been linked to a number of human pathologies, including neoplastic transformation, even though autophagy can also sustain the growth of tumor cells in certain contexts. In recent years, a considerable correlation has emerged between autophagy induction and stress-related cell-cycle responses, as well as unexpected roles for autophagy factors and selective autophagic degradation in the process of cell division. These advances have obvious implications for our understanding of the intricate relationship between autophagy and cancer. In this review, we will discuss our current knowledge of the reciprocal regulation connecting the autophagy pathway and cell-cycle progression. Furthermore, key findings involving nonautophagic functions for autophagy-related factors in cell-cycle regulation will be addressed.

show abstract

Uncovering the In Vivo Proxisome Using Proximity‐Tagging Methods

Santin

2019

BioEssays

View full text Add to dashboard Cite

The development of new approaches is critical to gain further insights into biological processes that cannot be obtained by existing methods or technologies. The detection of protein-protein interaction is often challenging, especially for weak and transient interactions or for membrane proteins. Over the last decade, several proximity-tagging methodologies have been developed to explore protein interactions in living cells. Among those, the most efficient are based on protein partner modification, such as biotinylation or pupylation. Such technologies are based on engineered variants of enzymes like peroxidases or ligases that release reactive molecules, in the presence of specific substrates, that bind surrounding proteins. Fusing a protein of interest (POI) to these enzymes allows the definition of an unbiased "proxisome," that is, all of the proteins in interaction or in close vicinity of the POI. Here, the different proximity-labeling tools available are described and comprehensive comparison to discuss advantages and limitations is provided.

show abstract

ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

Cited by 85 publications

References 64 publications

PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position

PRL-3 disrupts epithelial architecture by altering the post-mitotic midbody position

Autophagy and the Cell Cycle: A Complex Landscape

Uncovering the In Vivo Proxisome Using Proximity‐Tagging Methods

Contact Info

Product

Resources

About