Essential role of Fbxl14 ubiquitin ligase in regulation of vertebrate axis formation through modulating Mkp3 level

Zheng, Huakun; Du, Yiqin; Ye, Hua; Wu, Zhili; Yan, Yonggang; Li, Yiping

doi:10.1038/cr.2012.37

Cited by 8 publications

(6 citation statements)

References 11 publications

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“…FBXL14 has been reported to modulate ubiquitin-dependent proteolysis of Mkp3 (mitogen-activated protein kinase phosphatase 3) to regulate vertebrate axis formation in zebrafish (42), suggesting a possible role for SCF FBXL14 to function as a developmental timer. Because the mRNA level of Fbxl14 does not oscillate (Fig.…”

Section: Scf Fbxl14 Acts As the E3 Ubiquitin Ligase To Target Hes1 Fomentioning

confidence: 99%

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The E3 ubiquitin ligase SCFFBXL14 complex stimulates neuronal differentiation by targeting the Notch signaling factor HES1 for proteolysis

Chen¹,

Zhang

et al. 2017

Journal of Biological Chemistry

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Molecular oscillators are important cellular regulators of, for example, circadian clocks, oscillations of immune regulators, and short-period (ultradian) rhythms during embryonic development. The Notch signaling factor HES1 (hairy and enhancer of split 1) is a well-known repressor of proneural genes, and HES1 ultradian oscillation is essential for keeping cells in an efficiently proliferating progenitor state. HES1 oscillation is driven by both transcriptional self-repression and ubiquitin-dependent proteolysis. However, the E3 ubiquitin ligase targeting HES1 for proteolysis remains unclear. Based on siRNA-mediated gene silencing screening, co-immunoprecipitation, and ubiquitination assays, we discovered that the E3 ubiquitin ligase SCF complex regulates HES1 ubiquitination and proteolysis. siRNA-mediated knockdown of the Cullin-RING E3 ubiquitin ligases RBX1 or CUL1 increased HES1 protein levels, prolonged its half-life, and dampened its oscillation. FBXL14, an F-box protein for SCF ubiquitin ligase, associates with HES1. FBXL14 silencing stabilized HES1, whereas FBXL14 overexpression decreased HES1 protein levels. Of note, the SCF complex promoted the ubiquitination of HES1 , and a conserved WRPW motif in HES1 was essential for HES1 binding to FBXL14 and for ubiquitin-dependent HES1 degradation. HES1 knockdown promoted neuronal differentiation, but FBXL14 silencing inhibited neuronal differentiation induced by HES1 ablation in mES and F9 cells. Our results suggest that SCF promotes neuronal differentiation by targeting HES1 for ubiquitin-dependent proteolysis and that the C-terminal WRPW motif in HES1 is required for this process.

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Section: Scf Fbxl14 Acts As the E3 Ubiquitin Ligase To Target Hes1 Fomentioning

confidence: 99%

“…Its Xenopus homologue, Ppa, regulates expression of epithelial mesenchymal transition factors including Twist, Snai1, Slug, and Sip1 in the neural crest development of Xenopus laevis (41). FBXL14 is also essential for vertebrate axis formation in zebrafish (42). Deletion of FBXL14 has been reported to associate with the neurological disorders (43).…”

mentioning

confidence: 99%

The E3 ubiquitin ligase SCFFBXL14 complex stimulates neuronal differentiation by targeting the Notch signaling factor HES1 for proteolysis

Chen¹,

Zhang

et al. 2017

Journal of Biological Chemistry

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“…Deletion of FBXL14 was found to associate with the neurological disorders (Abdelmoity et al, 2011). FBXL14 is also essential for vertebrate axis formation in zebrafish (Zheng et al, 2012). As a tumor suppressor, FBXL14 has been shown to control Snail1, an essential regulator of the epithelial-mesenchymal transition under hypoxia condition.…”

Section: Introductionmentioning

confidence: 99%

Deubiquitinase USP13 maintains glioblastoma stem cells by antagonizing FBXL14-mediated Myc ubiquitination

Fang

Zhou

et al. 2016

Journal of Experimental Medicine

117

109

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“…There are 2 homologues of Fbxl14 in zebrafish, namely Fbxl14a and Fbxl14b that are differently regulators of dorsoventral patterning through the targeting of the MAP kinase phosphatase-3 (Mkp3). 93 Ppa is highly conserved across species, 94 in fact, the SCFFbxl14 ubiquitin ligase also targets Snail1 in mammalian cells (Fig. 2).…”

Section: Scf-ppa/fbxl14mentioning

confidence: 99%

Regulation of the protein stability of EMT transcription factors

Dı́az

Viñas-Castells

Herreros

2014

Cell Adhesion & Migration

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Essential role of Fbxl14 ubiquitin ligase in regulation of vertebrate axis formation through modulating Mkp3 level

Cited by 8 publications

References 11 publications

The E3 ubiquitin ligase SCFFBXL14 complex stimulates neuronal differentiation by targeting the Notch signaling factor HES1 for proteolysis

The E3 ubiquitin ligase SCFFBXL14 complex stimulates neuronal differentiation by targeting the Notch signaling factor HES1 for proteolysis

Deubiquitinase USP13 maintains glioblastoma stem cells by antagonizing FBXL14-mediated Myc ubiquitination

Regulation of the protein stability of EMT transcription factors

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