<scp>FBXL</scp>
            13 directs the proteolysis of
            <scp>CEP</scp>
            192 to regulate centrosome homeostasis and cell migration

Fung, Ella; Richter, Carmen; Yang, Hong-Bin; Schäffer, Isabell; Fischer, Román; Kessler, Benedikt M.; Bassermann, Florian; D’Angiolella, Vincenzo

doi:10.15252/embr.201744799

Cited by 22 publications

(23 citation statements)

References 37 publications

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“…There appeared to be a decrease in migration in the MDA-MB-231 cell line compared to the control, but this was not significant (Figure 10C). The area of the scratch was measured using the MRI Wound Healing Tool macro designed for ImageJ, as cited in recent papers [20,21]. Because of the general decrease in cellular migration, E-cadherin and N-cadherin levels were quantified (Figure 11).…”

Section: Resultsmentioning

confidence: 99%

Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells

Lewis

Jordan

Tollefsbol

2018

Cancers

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Triple-negative breast cancer comprises approximately 15–20% of all breast cancers diagnosed and is nearly twice as common in black women than white women in the United States. We evaluated the effects of two epigenetic-modifying compounds on markers of growth potential in several triple-negative breast cancer cell lines. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor currently used in the treatment of cutaneous T cell lymphoma, was administered to triple-negative breast cancer cells alone or in combination with epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor isolated from green tea. The compounds affected the expression of oncogenic miR-221/222 and tumor suppressors, p27 and PTEN, in addition to estrogen receptor alpha (ERα). E-cadherin expression was increased while N-cadherin was decreased, indicating a more epithelial phenotype. In addition, the activity of DNMTs was diminished with the treatments, and there was a significant enrichment of AcH3 within the promoter of p27 and PTEN, suggesting a role of epigenetic mechanisms for the aforementioned changes. These results translated to reduced migration of the triple-negative breast cancer cells with the treatments. Together, these findings support the role of SAHA and EGCG in limiting growth and proliferation of breast cancer cells.

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Section: Resultsmentioning

confidence: 99%

Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells

Lewis

Jordan

Tollefsbol

2018

Cancers

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“…Numerous lines of evidence demonstrate that SCF complex components promote the ubiquitination and degradation of regulatory proteins and play roles in tumorigenesis and progression 4 , 81 . The function of Skp1 is very important in cellular activities, including the ubiquitination of cell-cycle-related proteins 82 , kinetochore function, cell division 83 , 84 , and tumor formation 85 .…”

Section: The Ring Box Protein Rbx1 Adaptor Skp1 and F-box Proteins mentioning

confidence: 99%

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Shi¹,

Du²,

Peng³

et al. 2020

Oncogenesis

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Cullin (CUL) proteins have critical roles in development and cancer, however few studies on CUL7 have been reported due to its characteristic molecular structure. CUL7 forms a complex with the ROC1 ring finger protein, and only two F-box proteins Fbxw8 and Fbxw11 have been shown to bind to CUL7. Interestingly, CUL7 can interact with its substrates by forming a novel complex that is independent of these two F-box proteins. The biological implications of CUL-ring ligase 7 (CRL7) suggest that the CRL7 may not only perform a proteolytic function but may also play a non-proteolytic role. Among the existing studied CRL7-based E3 ligases, CUL7 exerts both tumor promotion and suppression in a context-dependent manner. Currently, the mechanism of CUL7 in cancer remains unclear, and no studies have addressed potential therapies targeting CUL7. Consistent with the roles of the various CRL7 adaptors exhibit, targeting CRL7 might be an effective strategy for cancer prevention and treatment. We systematically describe the recent major advances in understanding the role of the CUL7 E3 ligase in cancer and further summarize its potential use in clinical therapy.

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“…The expectation is that Nup188’s turnover is inhibited during G2 and early M-phase to elevate its levels and then stimulated at the end of mitosis to trigger its degradation. While we have not yet identified the molecular players that control this behavior, clear candidates are E3 ubiquitin ligases such as the anaphase-promoting complex or the SKP-CUL1-F Box complex, which have both been implicated in centrosome function by impacting the degradation of PCM components (Arquint et al, 2018; Cunha-Ferreira et al, 2009; D’Angiolella et al, 2010; Drosopoulos et al, 2014; Freed et al, 1999; Fung et al, 2018; Holland et al, 2010; Piva et al, 2002; Prosser et al, 2012). Other E3 ligases have also been implicated as functioning at centrosomes including Mib1 (Čajánek et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Differential turnover of Nup188 controls its levels at centrosomes and role in centriole duplication

Vishnoi

Dhanasekeran

Chalfant

et al. 2020

Journal of Cell Biology

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NUP188 encodes a scaffold component of the nuclear pore complex (NPC) and has been implicated as a congenital heart disease gene through an ill-defined function at centrioles. Here, we explore the mechanisms that physically and functionally segregate Nup188 between the pericentriolar material (PCM) and NPCs. Pulse-chase fluorescent labeling indicates that Nup188 populates centrosomes with newly synthesized protein that does not exchange with NPCs even after mitotic NPC breakdown. In addition, the steady-state levels of Nup188 are controlled by the sensitivity of the PCM pool, but not the NPC pool, to proteasomal degradation. Proximity-labeling and super-resolution microscopy show that Nup188 is vicinal to the inner core of the interphase centrosome. Consistent with this, we demonstrate direct binding between Nup188 and Cep152. We further show that Nup188 functions in centriole duplication at or upstream of Sas6 loading. Together, our data establish Nup188 as a component of PCM needed to duplicate the centriole with implications for congenital heart disease mechanisms.

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FBXL 13 directs the proteolysis of CEP 192 to regulate centrosome homeostasis and cell migration

Cited by 22 publications

References 37 publications

Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells

Effects of SAHA and EGCG on Growth Potentiation of Triple-Negative Breast Cancer Cells

The functional analysis of Cullin 7 E3 ubiquitin ligases in cancer

Differential turnover of Nup188 controls its levels at centrosomes and role in centriole duplication

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