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Trim37 plk4

WebJun 25, 2024 · We identify TRIM37 as a key mediator of growth arrest when PLK4 activity is partially or fully inhibited but is not required for growth arrest triggered by supernumerary centrosomes. Moreover, this activity is independent of its role as an E3 ligase and distinct from other TRIM37 functions described to date. WebTRIM37 controls cancer-specific vulnerability to PLK4 inhibition. Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer. TRIM37 has a role in …

Targeting TRIM37-driven centrosome dysfunction in 17q23 …

WebApr 11, 2024 · The ubiquitin ligase TRIM37 localizes to centrosomes, but its centrosomal roles are not yet defined. ... In Xenopus extracts, PLK4 … WebJun 27, 2024 · TRIM37 interacts with PLK4 and CEP192 ( Meitinger et al., 2024 ). Although TRIM37 can promote ubiquitination of PLK4, it is distinct from SCF β−TRCP modification since it does not result in changes to PLK4 abundance ( Meitinger et al., 2024 ). cornerstone way reno nv https://southadver.com

Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified ...

WebJul 1, 2024 · TRIM37 deletion restored the ability of cells to proliferate in centrinone. Thus, centrosome removal via Plk4 inhibition appears to be a promising strategy for … WebAug 5, 2024 · TRIM37 amplification has been observed in a large number of cancers, and synthetic lethality of PLK4 inhibitors in TRIM37-amplified breast cancer, which accounts for approximately 10% of breast cancers, has been confirmed [18, 19]. Therefore, inhibition of PLK4 using PLK4 small-molecule inhibitors provides a new approach to trigger selective ... WebSep 18, 2024 · When TRIM37 is more active, centrosomes do not behave correctly and errors occur during cell division, leading to the overactive cell division that results in tumors. 1 An enzyme called PLK4 kickstarts the errant cell division process in … fanshawe operations management

Design, synthesis, and biological evaluation of novel pyrazolo …

Category:Abstract 2633: Discovery of novel, highly selective inhibitors of PLK4 ...

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Trim37 plk4

Dong Kong - Staff Scientist - National Cancer Institute (NCI)

WebSpecifically, inhibition of polo-like kinase 4 (PLK4) using small molecules leads to centrosome depletion, which triggers mitotic catastrophe in cells that exhibit amplicon-directed overexpression of TRIM37. To explain this effect, we identify TRIM37 as a negative regulator of centrosomal pericentriolar material.

Trim37 plk4

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WebApr 11, 2024 · The ubiquitin ligase TRIM37 localizes to centrosomes, but its centrosomal roles are not yet defined. ... In Xenopus extracts, PLK4 assemblies additionally recruit … WebThus, TRIM37 is an essential determinant of mitotic vulnerability to PLK4 inhibition. Linkage of TRIM37 to prevalent cancer-associated genomic changes-including 17q gain in …

WebAug 5, 2024 · TRIM37 amplification has been observed in a large number of cancers, and synthetic lethality of PLK4 inhibitors in TRIM37-amplified breast cancer, which accounts … WebSep 9, 2024 · Extended Data Fig. 2 Inhibitor selectivity for PLK4—and not other kinases—is required for the synthetic lethal killing of cells overexpressing TRIM37. a, Representative …

WebFeb 20, 2015 · VA Directive 6518 4 f. The VA shall identify and designate as “common” all information that is used across multiple Administrations and staff offices to serve VA … WebThe PLKs comprise a protein family that has been identified as critical for spindle formation (26), centrosome duplication (27), and mitotic entry (28). PLK4 is the most structurally...

WebApr 4, 2024 · Request PDF Abstract 4998: Selective PLK4 inhibition demonstrates synthetic lethality in TRIM37 amplified neuroblastoma and breast cancer models while less selective inhibitors do not ...

WebTRIM37 interacts with and ubiquitinates PLK4 but does not alter PLK4 levels, suggesting that rather than promoting its degradation, TRIM37-mediated ubiquitination prevents the incorporation of PLK4 into ectopic assemblies ( Meitinger et al., 2024 ). cornerstone wealth advisory group scWebTo assess if elevated TRIM37 expression in cancers confers enhanced sensitivity to PLK4 inhibition, we analyzed two breast cancer (BT474 and MCF7) and four neuroblastoma … fanshawe ontarioWebNov 2, 2024 · TRIM37 exerted bidirectional control over mitosis in PLK4-inhibited cells. Whereas TRIM37 overexpression led to catastrophic mitotic failure in cells treated with a … cornerstone wealth management fort collinsWebFeb 1, 2024 · Interestingly, in 17q23-amplified cancers (such as breast cancers and glioblastoma) which have increased TRIM37, PLK4 inhibition cannot be compensated by acentriolar MTOCs promoting spindle assembly, thus leading to synthetic lethality through mitotic catastrophy –cell death occurring during or after aberrant mitosis [36 ••,37 ... fanshawe open programsWebSep 9, 2024 · Thus, TRIM37 is an essential determinant of mitotic vulnerability to PLK4 inhibition. Linkage of TRIM37 to prevalent cancer-associated genomic changes-including … cornerstone wealth group llcWebJun 27, 2024 · PLK4 activity decreases in a dose-dependent manner upon centrinone B addition. TRIM37 promotes PLK4 auto-phosphorylation (orange circles) outside the … cornerstone wealth management incWebJan 25, 2024 · TRIM37 is an E3 ubiquitin ligase mutated in Mulibrey nanism, a disease with impaired organ growth and increased tumor formation. TRIM37 depletion from tissue culture cells results in... fanshawe oral health clinic