Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90.
Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90.
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DOI：
10.1038/nchembio.670
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发表时间：
2011-09-25
影响因子：
14.8
通讯作者：
Chiosis, Gabriela
中科院分区：
文献类型：
--
作者：
Moulick, Kamalika;Ahn, James H.;Zong, Hongliang;Rodina, Anna;Cerchietti, Leandro;DaGama, Erica M. Gomes;Caldas-Lopes, Eloisi;Beebe, Kristin;Perna, Fabiana;Hatzi, Katerina;Vu, Ly P.;Zhao, Xinyang;Zatorska, Danuta;Taldone, Tony;Smith-Jones, Peter;Alpaugh, Mary;Gross, Steven S.;Pillarsetty, Nagavarakishore;Ku, Thomas;Lewis, Jason S.;Larson, Steven M.;Levine, Ross;Erdjument-Bromage, Hediye;Guzman, Monica L.;Nimer, Stephen D.;Melnick, Ari;Neckers, Len;Chiosis, Gabriela
大多数癌症的特征是多种分子改变，但目前还无法确定这些信号通路中涉及的关键蛋白质。我们发现，抑制剂PU-H71优先靶向肿瘤富集的Hsp90复合物，并亲和力捕获Hsp90依赖的致癌客户蛋白。我们使用PU-H71亲和力捕获设计了一种蛋白质组学方法，当结合生物信息学途径分析时，可以识别慢性髓性白血病中失调的信号网络和关键的癌蛋白。鉴定出的相互作用组与这种癌症中特征明确的改变的蛋白质组重叠，表明该方法可以提供对个体肿瘤生物学的全局见解，包括原发性患者标本。此外，我们表明这种方法可用于识别以前未表征的癌蛋白和机制，可能导致新的靶向治疗。我们进一步表明，富含pu - h71的Hsp90物种的丰度不是由Hsp90表达单独决定的，它可以预测细胞对Hsp90抑制的敏感性。
Most cancers are characterized by multiple molecular alterations, but identification of the key proteins involved in these signaling pathways is currently beyond reach. We show that the inhibitor PU-H71 preferentially targets tumor-enriched Hsp90 complexes and affinity captures Hsp90-dependent oncogenic client proteins. We have used PU-H71 affinity capture to design a proteomic approach that, when combined with bioinformatic pathway analysis, identifies dysregulated signaling networks and key oncoproteins in chronic myeloid leukemia. The identified interactome overlaps with the well-characterized altered proteome in this cancer, indicating that this method can provide global insights into the biology of individual tumors, including primary patient specimens. In addition, we show that this approach can be used to identify previously uncharacterized oncoproteins and mechanisms, potentially leading to new targeted therapies. We further show that the abundance of the PU-H71-enriched Hsp90 species, which is not dictated by Hsp90 expression alone, is predictive of the cell’s sensitivity to Hsp90 inhibition.
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影响因子：
11.2
作者：
Maloney, Alison;Clarke, Paul A.;Workman, Paul
通讯作者：
Workman, Paul
影响因子：
64.8
作者：
Naka, Kazuhito;Hoshii, Takayuki;Hirao, Atsushi
通讯作者：
Hirao, Atsushi
DOI：
10.1124/jpet.109.162669
发表时间：
2010-05-01
影响因子：
3.5
作者：
Jaganathan, Soumya;Yue, Peibin;Turkson, James
通讯作者：
Turkson, James
影响因子：
64.8
作者：
Ley, Timothy J.;Mardis, Elaine R.;Ding, Li;Fulton, Bob;McLellan, Michael D.;Chen, Ken;Dooling, David;Dunford-Shore, Brian H.;McGrath, Sean;Hickenbotham, Matthew;Cook, Lisa;Abbott, Rachel;Larson, David E.;Koboldt, Dan C.;Pohl, Craig;Smith, Scott;Hawkins, Amy;Abbott, Scott;Locke, Devin;Hillier, LaDeana W.;Miner, Tracie;Fulton, Lucinda;Magrini, Vincent;Wylie, Todd;Glasscock, Jarret;Conyers, Joshua;Sander, Nathan;Shi, Xiaoqi;Osborne, John R.;Minx, Patrick;Gordon, David;Chinwalla, Asif;Zhao, Yu;Ries, Rhonda E.;Payton, Jacqueline E.;Westervelt, Peter;Tomasson, Michael H.;Watson, Mark;Baty, Jack;Ivanovich, Jennifer;Heath, Sharon;Shannon, William D.;Nagarajan, Rakesh;Walter, Matthew J.;Link, Daniel C.;Graubert, Timothy A.;DiPersio, John F.;Wilson, Richard K.
通讯作者：
Wilson, Richard K.
影响因子：
16
作者：
Bedford, Mark T.;Clarke, Steven G.
通讯作者：
Clarke, Steven G.