In:
The EMBO Journal, EMBO, Vol. 36, No. 9 ( 2017-05-02), p. 1243-1260
Abstract:
image Aberrant activation of PRC 2 can block expression of key tumor suppressors and contribute to oncogenesis. The discovery of a drug that triggers specific degradation of PRC 2 component EZH 2 offers a new therapeutic strategy for cancer treatment. Derivatives of gambogenic acid ( GNA ) represent a new and unique category of EZH 2 inhibitors. GNA ‐derivatives bind covalently to EZH 2, but not other methyltransferases, and trigger its degradation. The E3 ubiquitin ligase CHIP governs ubiquitination and destruction of EZH 2 oncoprotein upon covalent binding of GNA derivatives. GNA derivatives efficiently inhibit cancer growth in vivo while showing little toxic side effect.
Type of Medium:
Online Resource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.201694058
Language:
English
Publisher:
EMBO
Publication Date:
2017
detail.hit.zdb_id:
1467419-1
detail.hit.zdb_id:
586044-1
SSG:
12
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