FBXL5 modulates HIF-1α transcriptional activity by degradation of CITED2

Machado-Oliveira, Gisela; Guerreiro, Eduarda; Matias, Ana Catarina; Facucho-Oliveira, João; Pacheco-Leyva, Ivette; Bragança, José

doi:10.1016/j.abb.2015.04.012

Cited by 22 publications

(23 citation statements)

References 56 publications

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“…CITED2 has high affinity for p300/CBP and competes with HIF1α for binding, thus it can inhibit hypoxic signalling. It has recently been described that SCF(Fbxl5) can ubiquitinate and cause the degradation of CITED2, and thus its overexpression might aid tumour formation by increasing HIF1α transcription (233). Another E3 ligase shown to ubiquitinate and cause the degradation of HIF1α under hypoxic conditions, after its phosphorylation by GSK3β, is SCF(Fbxw7) ligase (234).…”

Section: Angiogenesismentioning

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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Section: Angiogenesismentioning

confidence: 98%

F-box protein interactions with the hallmark pathways in cancer

Randle

Laman

2016

Seminars in Cancer Biology

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“…Overexpression of miR-290-295 promotes the entry of S phase from G1 phase, indicating that this cell cycle process may be controlled by the substrate of miR-290-295, FBXL5 (Lichner, Pall, 2011). Another independent study revealed that FBXL5 targets CITED2 (with Glu/Asp-Rich Carboxy-Terminal Domain, 2) for degradation to regulate the HIF-1α (hypoxia-inducible factor-1α) (Machado-Oliveira et al, 2015). Moreover, Snail 1 is validated as a substrate of FBXL5 and the degradation of Snail 1 leads to inhibition of metastasis in gastric cancer cells (Vinas-Castells et al, 2014, Wu et al, 2015).…”

Section: Roles Of Fbxl Sub-family In Cell Cyclementioning

confidence: 99%

Ubiquitination-mediated degradation of cell cycle-related proteins by F-box proteins

Zheng

Wang

Wei

2016

The International Journal of Biochemistry & Cell Biology

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F-box proteins, subunits of SKP1-cullin 1-F-box protein (SCF) type of E3 ubiquitin ligase complexes, have been validated to play a crucial role in governing various cellular processes such as cell cycle, cell proliferation, apoptosis, migration, invasion and metastasis. Recently, a wealth of evidence has emerged that F-box proteins is critically involved in tumorigenesis in part through governing the ubiquitination and subsequent degradation of cell cycle proteins, and dysregulation of this process leads to aberrant cell cycle progression and ultimately, tumorigenesis. Therefore, in this review, we describe the critical role of F-box proteins in the timely regulation of cell cycle. Moreover, we discuss how F-box proteins involve in tumorigenesis via targeting cell cycle-related proteins using biochemistry studies, engineered mouse models, and pathological gene alternations. We conclude that inhibitors of F-box proteins could have promising therapeutic potentials in part through controlling of aberrant cell cycle progression for cancer therapies.

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“…Myc-ISL1 was co-immunoprecipitated with flag-CITED2, implying that ISL1 and CITED2 were in protein complexes in HEK293T cells. We also visualized ISL1-CITED2 interaction in living cells using vectors expressing either ISL1 in fusion with the N-terminal domain of the fluorescent protein VENUS (VEN-ISL1), CITED2 in fusion with the C-terminal domain of VENUS (VEC-CITED2), or control vectors to perform bifluorescence complementation (BiFC) assays (Machado-Oliveira et al., 2015). The co-transfection of VEN-ISL1 and VEC-CITED2 in E14/T cells resulted in a specific detection of fluorescence, confirming that ISL1 and CITED2 associate in these cells (Figures 5C and S3).…”

Section: Resultsmentioning

confidence: 99%

“…For in vitro binding assays, GST-CITED2 fusion proteins and in vitro translated myc-ISL1 were prepared as previously described (Machado-Oliveira et al., 2015). Myc-ISL1 expression plasmid was constructed in pcDNA3 (Invitrogen) with an amino-terminal myc epitope tag.…”

Section: Methodsmentioning

confidence: 99%

CITED2 Cooperates with ISL1 and Promotes Cardiac Differentiation of Mouse Embryonic Stem Cells

et al. 2016

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SummaryThe transcriptional regulator CITED2 is essential for heart development. Here, we investigated the role of CITED2 in the specification of cardiac cell fate from mouse embryonic stem cells (ESC). The overexpression of CITED2 in undifferentiated ESC was sufficient to promote cardiac cell emergence upon differentiation. Conversely, the depletion of Cited2 at the onset of differentiation resulted in a decline of ESC ability to generate cardiac cells. Moreover, loss of Cited2 expression impairs the expression of early mesoderm markers and cardiogenic transcription factors (Isl1, Gata4, Tbx5). The cardiogenic defects in Cited2-depleted cells were rescued by treatment with recombinant CITED2 protein. We showed that Cited2 expression is enriched in cardiac progenitors either derived from ESC or mouse embryonic hearts. Finally, we demonstrated that CITED2 and ISL1 proteins interact physically and cooperate to promote ESC differentiation toward cardiomyocytes. Collectively, our results show that Cited2 plays a pivotal role in cardiac commitment of ESC.

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FBXL5 modulates HIF-1α transcriptional activity by degradation of CITED2

Cited by 22 publications

References 56 publications

F-box protein interactions with the hallmark pathways in cancer

F-box protein interactions with the hallmark pathways in cancer

Ubiquitination-mediated degradation of cell cycle-related proteins by F-box proteins

CITED2 Cooperates with ISL1 and Promotes Cardiac Differentiation of Mouse Embryonic Stem Cells

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