IndraLab

Statements


COPS6 activates CUL1. 7 / 7
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"35 Interestingly, CSN6 can increase CUL1 neddylation."

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"We then found that increasing amounts of CSN6 enhanced neddylation of wild type Cullin-1 but not the Cullin-1 mutant 41 in which the Nedd-8-conjugating site lysine (K) 720 was mutated to arginine (R) (XREF_SUPPLEMENTARY)."

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"CSN6 knockdown reduced the neddylated form of Cullin-1, leading to accumulation of Fbxw7, which in turn caused downregulation of Myc (XREF_FIG)."

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"We further showed that overexpression of dominant negative Ubc12 (dnUbc12-HA) XREF_BIBR, XREF_BIBR, which antagonized CSN6 mediated increase of Cullin-1 neddylation, compromised CSN6 mediated Fbxw7alpha downregulation (XREF_FIG)."

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"On the other hand, mono-allelic deletion of CSN6 decreases Cullin1 neddylation, stabilizes FBXW7, and compromises lymphomagenesis in an Emu-Myc mouse model [XREF_BIBR]."

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"Together, these data suggest that CSN6 increases Cullin-1 neddylation by competing with CSN5 for binding to Cullin-1 through the MPN domain, thereby facilitating Cullin-1-enhanced Fbxw7 degradation."

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"CSN6 enhanced neddylation of Cullin-1 and facilitated auto-ubiquitination and degradation of Fbxw7, a component of CRL involved in Myc ubiquitination, thereby stabilizing Myc."