APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis

Schrock, Morgan S.; Stromberg, Benjamin R.; Scarberry, Luke; Summers, Matthew K.

doi:10.1016/j.semcancer.2020.03.001

Cited by 65 publications

(74 citation statements)

References 188 publications

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“…Interestingly, this ectopic expression was able to increase cell viability and had a growth-prompting effect. Additionally, the forced expression of RIZ2 caused the deregulation of several genes involved in mitosis, including the overexpression of genes coding for Cyclin B and for some subunits of the Anaphase-Promoting Complex/Cyclosome (APC/C), which are often dysregulated during tumorigenesis (67). Accordingly, cell cycle analysis showed that RIZ2 could facilitate the G2-to-M phase transition.…”

Section: Discussionmentioning

confidence: 99%

Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models

et al. 2021

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Positive Regulatory Domain (PRDM) gene family members commonly express two main molecular variants, the PR-plus isoform usually acting as tumor suppressor and the PR-minus one functioning as oncogene. Accordingly, PRDM2/RIZ encodes for RIZ1 (PR-plus) and RIZ2 (PR-minus). In human cancers, genetic or epigenetic modifications induce RIZ1 silencing with an expression level imbalance in favor of RIZ2 that could be relevant for tumorigenesis. Additionally, in estrogen target cells and tissues, estradiol increases RIZ2 expression level with concurrent increase of cell proliferation and survival. Several attempts to study RIZ2 function in HeLa or MCF-7 cells by its over-expression were unsuccessful. Thus, we over-expressed RIZ2 in HEK-293 cells, which are both RIZ1 and RIZ2 positive but unresponsive to estrogens. The forced RIZ2 expression increased cell viability and growth, prompted the G2-to-M phase transition and organoids formation. Accordingly, microarray analysis revealed that RIZ2 regulates several genes involved in mitosis. Consistently, RIZ silencing in both estrogen-responsive MCF-7 and -unresponsive MDA-MB-231 cells induced a reduction of cell proliferation and an increase of apoptosis rate. Our findings add novel insights on the putative RIZ2 tumor-promoting functions, although additional attempts are warranted to depict the underlying molecular mechanism.

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Section: Discussionmentioning

confidence: 99%

Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models

et al. 2021

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“…Cdh1 is found dysregulated in breast cancer and melanoma, and triggers genome instability and weakens DNA damage response [ 50 ]. Cdh1 is also shown to delay G1 to S transition in cell cycle regulation, suggesting its role in tumorigenesis [ 70 ].…”

Section: Ubiquitin Ligasesmentioning

confidence: 99%

Dysregulation of the Ubiquitin Proteasome System in Human Malignancies: A Window for Therapeutic Intervention

Fhu

Ali

2021

Cancers

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The ubiquitin proteasome system (UPS) governs the non-lysosomal degradation of oxidized, damaged, or misfolded proteins in eukaryotic cells. This process is tightly regulated through the activation and transfer of polyubiquitin chains to target proteins which are then recognized and degraded by the 26S proteasome complex. The role of UPS is crucial in regulating protein levels through degradation to maintain fundamental cellular processes such as growth, division, signal transduction, and stress response. Dysregulation of the UPS, resulting in loss of ability to maintain protein quality through proteolysis, is closely related to the development of various malignancies and tumorigenesis. Here, we provide a comprehensive general overview on the regulation and roles of UPS and discuss functional links of dysregulated UPS in human malignancies. Inhibitors developed against components of the UPS, which include U.S. Food and Drug Administration FDA-approved and those currently undergoing clinical trials, are also presented in this review.

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“…APC/C is an evolutionarily conserved E3 ubiquitin ligase. Its main function is to trigger the transition from metaphase to anaphase during mitosis, which plays a key role in cell division, making it crucial for cellular survival and development ( Schrock et al, 2020 ). The ubiquitin ligase APC/C-Cdk-1 can promote ubiquitination and degradation of PFKFB3, thus reducing glycolysis flux, and then generally reducing the number of cells in S phase and inhibiting cell proliferation ( Almeida et al, 2010 ).…”

Section: The Role Of Pfkfb3 In Ecs and Angiogenesismentioning

confidence: 99%

PFKFB3: A Potential Key to Ocular Angiogenesis

Zhou

Wang

et al. 2021

Front. Cell Dev. Biol.

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The current treatment for ocular pathological angiogenesis mainly focuses on anti-VEGF signals. This treatment has been confirmed as effective despite the unfavorable side effects and unsatisfactory efficiency. Recently, endothelial cell metabolism, especially glycolysis, has been attracting attention as a potential treatment by an increasing number of researchers. Emerging evidence has shown that regulation of endothelial glycolysis can influence vessel sprouting. This new evidence has raised the potential for novel treatment targets that have been overlooked for a long time. In this review, we discuss the process of endothelial glycolysis as a promising target and consider regulation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as treatment for ocular pathological angiogenesis.

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APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis

Cited by 65 publications

References 188 publications

Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models

Searching for a Putative Mechanism of RIZ2 Tumor-Promoting Function in Cancer Models

Dysregulation of the Ubiquitin Proteasome System in Human Malignancies: A Window for Therapeutic Intervention

PFKFB3: A Potential Key to Ocular Angiogenesis

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