FBH1 protects melanocytes from transformation and is deregulated in melanomas

Jeong, Yeong-Ho; Cermak, Laird S.; Guijarro, María V.; Hernando, Eva; Pagano, Michele

doi:10.4161/cc.24165

Cited by 19 publications

(14 citation statements)

References 13 publications

(16 reference statements)

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“…Similarly, FBXO18 is often deleted or mutated in melanoma cells, and the depletion of FBXO18 enhances ultraviolet (UV)-mediated transformation of human melanocytes, which suggests a tumoursuppressive role of FBXO18 (REF. 69). Multiple studies have shown that FBXO31 is downregulated in human breast cancer and hepatocellular carcinoma cell lines 70,71 .…”

Section: Tumour-suppressive F-box Proteinsmentioning

confidence: 99%

Roles of F-box proteins in cancer

et al. 2014

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F-box proteins, which are the substrate-recognition subunits of SKP1–cullin 1–F-box protein (SCF) E3 ligase complexes, have pivotal roles in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins. Dysregulation of F-box protein-mediated proteolysis leads to human malignancies. Notably, inhibitors that target F-box proteins have shown promising therapeutic potential, urging us to review the current understanding of how F-box proteins contribute to tumorigenesis. As the physiological functions for many of the 69 putative F-box proteins remain elusive, additional genetic and mechanistic studies will help to define the role of each F-box protein in tumorigenesis, thereby paving the road for the rational design of F-box protein-targeted anticancer therapies.

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Section: Tumour-suppressive F-box Proteinsmentioning

confidence: 99%

Roles of F-box proteins in cancer

et al. 2014

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“…Interestingly, a second E3 ligase, Cul4(Cdt2) has been shown to degrade Fbxo18, thus limiting its anti-recombinase activity and promoting DNA repair (165). Cells deficient for Fbxo18 are defective in responding to DSB and therefore manage to survive replication stress but probably accumulate mutations (166,167). In addition to interacting with Rad51, Fbxo18 has multiple enzymatic activities.…”

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confidence: 98%

F-box protein interactions with the hallmark pathways in cancer

Randle

Laman

2016

Seminars in Cancer Biology

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F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)-type E3 ubiquitin ligases and are responsible for directing the ubiquitination of numerous proteins essential for cellular function. Due to their ability to regulate the expression and activity of oncogenes and tumour suppressor genes, FBPs themselves play important roles in cancer development and progression. In this review, we provide a comprehensive overview of FBPs and their targets in relation to their interaction with the hallmarks of cancer cell biology, including the regulation of proliferation, epigenetics, migration and invasion, metabolism, angiogenesis, cell death and DNA damage responses. Each cancer hallmark is revealed to have multiple FBPs which converge on common signalling hubs or response pathways. We also highlight the complex regulatory interplay between SCF-type ligases and other ubiquitin ligases. We suggest six highly interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible candidates for therapeutic intervention.

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“…One study discovered that FBXO18 promotes DNA double-strand breakage and apoptosis upon DNA replication stress via regulation of activation of ATM and DNA-PK and phosphorylation of RPA2 and p53 [186]. Moreover, it has been reported that FBXO18 is often deleted in melanomas to protect melanoma cells from apoptosis [187]. …”

Section: F-box Proteinsmentioning

confidence: 99%

Recent advances in SCF ubiquitin ligase complex: Clinical implications

Zheng

Zhou

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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F-box proteins, which are subunit recruiting modules of SCF (SKP1-Cullin 1-F-box protein) E3 ligase complexes, play critical roles in the development and progression of human malignancies through governing multiple cellular processes including cell proliferation, apoptosis, invasion and metastasis. Moreover, there are emerging studies that lead to the development of F-box proteins inhibitors with promising therapeutic potential. In this article, we describe how F-box proteins including but not restricted to well-established Fbw7, Skp2 and β-TRCP, are involved in tumorigenesis. However, in-depth investigation is required to further explore the mechanism and the physiological contribution of undetermined F-box proteins in carcinogenesis. Lastly, we suggest that targeting F-box proteins could possibly open new avenues for the treatment and prevention of human cancers.

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FBH1 protects melanocytes from transformation and is deregulated in melanomas

Cited by 19 publications

References 13 publications

Roles of F-box proteins in cancer

Roles of F-box proteins in cancer

F-box protein interactions with the hallmark pathways in cancer

Recent advances in SCF ubiquitin ligase complex: Clinical implications

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