Regulating PLK1 dynamics by Cullin3/KLHL22-mediated ubiquitylation

Beck, Jochen; Peter, Matthias

doi:10.4161/cc.25839

Cited by 11 publications

(11 citation statements)

References 8 publications

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“…On the other hand, when the CUL3-based ubiquitin ligase was suppressed by either KLHL22 or CUL3 siRNA, we observed a significant increase of Plk1 staining on the kinetochores ( Fig. 2, A and B ), which is consistent with previously reported results ( Beck and Peter, 2013 ; Beck et al, 2013 ). Furthermore, to investigate whether Usp16 counteracts CUL3-based ubiquitination, we simultaneously knocked down both Usp16 and KLHL22 and found that the staining of Plk1 on the kinetochore remained largely stable ( Fig.…”

Section: Resultssupporting

confidence: 93%

“…As ubiquitination promotes the removal of Plk1 from the kinetochores ( Beck and Peter, 2013 ; Beck et al, 2013 ), we suspected that down-regulation of Usp16 would result in increased Plk1 ubiquitination and promote the removal of Plk1 from the kinetochores. Indeed, after Usp16 knockdown, we observed a dramatic decrease of Plk1 staining on the kinetochores in prometaphase cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…During the G2 to M phase transition, a portion of Plk1 localizes to the kinetochores, which is mediated by polo box domain (PBD)–mediated binding to kinetochore-localized interacting proteins ( Elia et al, 2003 ; Baumann et al, 2007 ; Lee et al, 2008a ,b ), and regulates the initiation of kinetochore–microtubule attachments for proper chromosome alignment ( Lampson and Kapoor, 2005 ; Kang et al, 2006 ; Nishino et al, 2006 ; Qi et al, 2006 ; Elowe et al, 2007 ; Li et al, 2010 ; Liu et al, 2012a ,b ; Mondal et al, 2012 ) to achieve accurate chromosome segregation into the daughter cells in mitosis ( Khodjakov et al, 1999 ; Clarke and Bachant, 2008 ; Amaro et al, 2010 ; Maia et al, 2012 ). Once chromosomes are properly aligned and spindle checkpoint is satisfied, this portion of Plk1 is ubiquitinated by cullin 3 (CUL3)–based E3 ligase at K492 within PBD, leading to the removal of Plk1 from the kinetochores most likely because of weakened binding between Plk1 and its interacting proteins localized on the kinetochores ( Beck and Peter, 2013 ; Beck et al, 2013 ). To prevent premature removal of Plk1 from the kinetochores and ensure the proper alignment of chromosomes, it is most likely that a yet-to-be-identified deubiquitination mechanism promotes the recruitment of Plk1 to, and its retention on, the kinetochores by antagonizing the function of the CUL3-based E3 ligase in early mitosis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

Zhuo

Guo

Zhang

et al. 2015

Journal of Cell Biology

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

Zhuo

Guo

Zhang

et al. 2015

Journal of Cell Biology

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“…KLHL complexes have been shown to ubiquitylate a number of mitotic protein kinases. KLHL9/13 and KLHL21 non-redundantly ubiquitylate Aurora B [ 10 , 11 ], whereas KLHL18 and KLHL22 target Aurora A [ 12 ] and PLK1 (Polo-like kinase 1) [ 13 ] respectively. KLHL function is also linked to several human cancers.…”

Section: Cullin-3-based Crls Employ Btb Domain Proteins As Substrate-mentioning

confidence: 99%

New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases

Canning

Bullock

2014

Biochemical Society Transactions

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E3 ubiquitin ligases that direct substrate proteins to the ubiquitin–proteasome system are promising, though largely unexplored drug targets both because of their function and their remarkable specificity. CRLs [Cullin–RING (really interesting new gene) ligases] are the largest group of E3 ligases and function as modular multisubunit complexes constructed around a Cullin-family scaffold protein. The Cul3-based CRLs uniquely assemble with BTB (broad complex/tramtrack/bric-à-brac) proteins that also homodimerize and perform the role of both the Cullin adapter and the substrate-recognition component of the E3. The most prominent member is the BTB–BACK (BTB and C-terminal Kelch)–Kelch protein KEAP1 (Kelch-like ECH-associated protein 1), a master regulator of the oxidative stress response and a potential drug target for common conditions such as diabetes, Alzheimer's disease and Parkinson's disease. Structural characterization of BTB–Cul3 complexes has revealed a number of critical assembly mechanisms, including the binding of an N-terminal Cullin extension to a bihelical ‘3-box’ at the C-terminus of the BTB domain. Improved understanding of the structure of these complexes should contribute significantly to the effort to develop novel therapeutics targeted to CRL3-regulated pathways.

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“…3 It has been reported that KLHL22 could regulate the ubiquitylation of PLK1 with Cullin 3 (CUL3) to influence the regulator of mitosis and control chromosome alignment. 4 In addition, it could bind to or regulate some other kinases, such as Nek2 and CDK1, that influence kinetochore-microtubule attachment and other mitotic processes at multiple levels, which means that KLHL22 may regulate cancer cell progression. 5 However, little is known regarding the function of KLHL22 in controlling CRC progression.…”

Section: Introductionmentioning

confidence: 99%

<p>KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway</p>

Song¹,

Yuan²,

Wang³

et al. 2020

CMAR

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Background: Colorectal cancer (CRC) is one of the most common aggressive malignancies. KLHL22 functions as a tumor suppressor, and previous findings have demonstrated that KLHL22 can regulate the development of breast cancer and CRC. However, few studies have investigated the role of KLHL22 in CRC cell epithelial-to-mesenchymal transition (EMT) and proliferation. The current study aimed to detect the role of KLHL22 in CRC cell proliferation and EMT and to elucidate the probable molecular mechanisms through which KLHL22 is involved with these processes. Materials and Methods: Transwell invasion, MTT, immunohistochemistry and Western blotting assays were performed to evaluate the migration, invasion and proliferation abilities of CRC cells, and the levels of active molecules involved in the Wnt/β-catenin signaling pathway were examined through Western blotting analysis. In addition, the in vivo function of KLHL22 was assessed using a tumor xenograft model. Results: KLHL22 expression was weaker in CRC tissues than in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation in vitro. Furthermore, the regulatory effects of KLHL22 on EMT were partially attributed to the Wnt/β-catenin signaling pathway. The in vivo results also showed that KLHL22 modulated CRC tumorigenesis. Conclusion: KLHL22 can regulate the activity of GSK-3β to influence the level of PI3K, and this regulation promotes EMT inhibition partially through the Wnt/β-catenin signaling pathway.

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Regulating PLK1 dynamics by Cullin3/KLHL22-mediated ubiquitylation

Cited by 11 publications

References 8 publications

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

New strategies to inhibit KEAP1 and the Cul3-based E3 ubiquitin ligases

<p>KLHL22 Regulates the EMT and Proliferation in Colorectal Cancer Cells in Part via the Wnt/β-Catenin Signaling Pathway</p>

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