Small-molecule control of intracellular protein levels through modulation of the ubiquitin proteasome system.
Small-molecule control of intracellular protein levels through modulation of the ubiquitin proteasome system.
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DOI：
10.1002/anie.201307761
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发表时间：
2014-02-24
影响因子：
16.6
通讯作者：
Crews, Craig M.
中科院分区：
文献类型：
--
作者：
Buckley, Dennis L.;Crews, Craig M.
传统上，生物学问题和药物针对蛋白质（例如酶和受体）的活性很容易被小分子控制。 ，蛋白质水平而不是蛋白质活性可以靶向，而靶向蛋白酶体的数量可以导致全球增加针对UPS的其他成分（例如，数百个E3泛素连接酶）的蛋白质水平会导致蛋白质水平的增加，以更具针对性的方式UPS的小分子调节剂具有诱导和抑制靶蛋白降解的能力酶和接收器。
Traditionally, biological probes and drugs have targeted the activities of proteins (such as enzymes and receptors) that can be easily controlled by small molecules. The remaining majority of the proteome has been deemed “undruggable”. By using small molecule modulators of the ubiquitin proteasome, protein levels, rather than protein activities can be targeted instead, increasing the number of druggable targets. While targeting the proteasome itself can lead to a global increase in protein levels, targeting other components of the UPS (e.g., the hundreds of E3 ubiquitin ligases) can lead to an increase in protein levels in a more targeted fashion. Alternatively, multiple strategies for inducing protein degradation with small molecule probes are emerging. With the ability to induce and inhibit the degradation of targeted proteins, small molecule modulators of the UPS have the potential to significantly expand the druggable portion of the proteome beyond traditional targets such as enzymes and receptors.
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影响因子：
7.3
作者：
Cai Q;Sun H;Peng Y;Lu J;Nikolovska-Coleska Z;McEachern D;Liu L;Qiu S;Yang CY;Miller R;Yi H;Zhang T;Sun D;Kang S;Guo M;Leopold L;Yang D;Wang S
通讯作者：
Wang S
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
16
作者：
Brownell, James E.;Sintchak, Michael D.;Dick, Lawrence R.
通讯作者：
Dick, Lawrence R.
DOI：
10.1073/pnas.0903392106
发表时间：
2009-05-19
影响因子：
11.1
作者：
Caldas-Lopes, Eloisi;Cerchietti, Leandro;Chiosis, Gabriela
通讯作者：
Chiosis, Gabriela
影响因子：
--
作者：
Bogyo, M;Shin, S;Ploegh, HL
通讯作者：
Ploegh, HL