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CUL7 inhibits KCNH1. 14 / 14
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"Multiple lines of biochemical, cell biological, and pharmacological evidence support the notion that 14-3-3 proteins facilitate Eag1 degradation mediated by Cul7, but not MKRN1."
36717938
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"Our findings demonstrate a chaperone-like role of 14-3-3 in Cul7-mediated Eag1 protein degradation."
36717938
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"14-3-3 proteins regulate cullin 7-mediated Eag1 degradation."
36717938
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"We have previously demonstrated that the multisubunit E3 ubiquitin ligase CUL7 promotes degradation of both ER localized immature and plasma-membrane-localized mature Eag1 proteins."
33647316
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"Cul7 mediates proteasomal and lysosomal degradation of Eag1 protein, whereas over-expression of 14-3-3 notably reduces Eag1 channel activity."
36717938
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"Therefore, one potential mechanism underlying the enhancement of Eag1 protein level by difopein/BV02 is that endogenous 14–3-3 proteins may contribute to Eag1 degradation by Cul7, which in turn is hindered by inhibition of 14-3-3 function with difopein/BV02."
36717938
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"To address this intriguing hypothesis, we went on to examine whether difopein co-expression may affect Cul7-mediated degradation of Eag1 proteins.Consistent with its known degradative effect on Eag1, Cul7 over-expression resulted in notable reduction of Eag1 protein level in HEK293T cells (Fig. 8A), whereas siRNA knock-down of endogenous Cul7 expression led to more than four-fold increase in Eag1 protein level (Fig. 8B)."
36717938
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"12 and 13 are in agreement with the notion that 14-3-3θ homodimer may regulate Cul7-mediated Eag1 degradation by facilitating the direct interaction between Cul7 E3 ligase complexes and Eag1 subunits.Previous studies of 14-3-3 oligomerization suggest that both homo- and hetero-dimerization are crucial for 14-3-3 scaffolding function with substrate proteins [55]."
36717938
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"It remains to be determined, therefore, whether various 14-3-3 isoforms may regulate Cul7-mediated Eag1 degradation in the form of homodimers or heterodimers."
36717938
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"Given the chaperone-like role of 14-3-3 proteins in promoting Cul7-mediated Eag1 degradation, it will be interesting to explore the tumor suppression potential of 14-3-3-targeting chemicals in Eag1-expressing cancers.Mutations in the genes encoding human Eag1 K channel have been linked to the congenital neurodevelopmental anomalies TMBTS and ZLS [7–9]."
36717938
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"Taken together, we propose that endogenous 14-3-3 proteins promote Cul7-mediated proteasomal and lysosomal degradation of immature and mature Eag1 proteins, respectively.E3 ubiquitin ligases such as parkin and TRIM25 are subject to 14-3-3-mediated auto-ubiquitination [44, 45]."
36717938
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"To ascertain the mechanistic role of 14-3-3 proteins in Cul7-mediated degradation of Eag1, we asked whether inhibition of endogenous 14-3-3 function with difopein may affect the interaction between Eag1 and Cul7."
36717938
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"Suppression of endogenous 14-3-3 function with difopein, BV02, or specific RNA interference significantly attenuated the extent of Cul7-mediated Eag1 degradation, and that Cul7 knock-down practically eradicated the effect of difopein on Eag1 protein level."
36717938
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"Cullin 7 mediates proteasomal and lysosomal degradations of rat Eag1 potassium channels."
28098200