Extensive protein dosage compensation in aneuploid human cancers.
Extensive protein dosage compensation in aneuploid human cancers.
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非整倍体人类癌症中的广泛蛋白剂量补偿。
DOI：
10.1101/gr.276378.121
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发表时间：
2022-07
期刊：
影响因子：
7
通讯作者：
Sheltzer, Jason M.
中科院分区：
文献类型：
--
作者：
Schukken, Klaske M.;Sheltzer, Jason M.
非整倍体是人类癌症的标志，但非整倍体对蛋白质表达的影响仍然知之甚少。为了揭示染色体拷贝数变化如何影响癌症蛋白质组，我们对数百种人类癌细胞系和肿瘤进行了分析，这些细胞系和肿瘤具有匹配的拷贝数，RNA表达和蛋白质表达数据。我们发现，大多数蛋白质显示剂量补偿，并且不能根据单独的染色体拷贝数预期的程度改变。我们发现了各种基因组，包括蛋白质复合物亚基和细胞周期基因，这些基因组在染色体获得和丢失时反复缓冲。几个遗传和生物物理因素预测蛋白质缓冲，突出复杂的翻译后调节机制，保持适当的基因产物剂量。最后，我们确定染色体非整倍性对癌基因和肿瘤抑制因子的表达具有中等影响，表明这些关键的癌症驱动因素也可以受到剂量补偿。总的来说，我们对癌症的非整倍性和剂量补偿的综合分析将有助于确定在改变的染色体上编码的关键驱动基因，并将揭示肿瘤发展过程中非整倍性的总体后果。
Aneuploidy is a hallmark of human cancers, but the effects of aneuploidy on protein expression remain poorly understood. To uncover how chromosome copy number changes influence the cancer proteome, we conducted an analysis of hundreds of human cancer cell lines and tumors with matched copy number, RNA expression, and protein expression data. We found that a majority of proteins show dosage compensation and fail to change by the degree expected based on chromosome copy number alone. We uncovered a variety of gene groups that were recurrently buffered upon both chromosome gain and loss, including protein complex subunits and cell cycle genes. Several genetic and biophysical factors were predictive of protein buffering, highlighting complex post-translational regulatory mechanisms that maintain appropriate gene product dosage. Finally, we established that chromosomal aneuploidy has a moderate effect on the expression of oncogenes and tumor suppressors, showing that these key cancer drivers can be subject to dosage compensation as well. In total, our comprehensive analysis of aneuploidy and dosage compensation across cancers will help identify the key driver genes encoded on altered chromosomes and will shed light on the overall consequences of aneuploidy during tumor development.
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影响因子：
4.4
作者：
Dürrbaum M;Kuznetsova AY;Passerini V;Stingele S;Stoehr G;Storchová Z
通讯作者：
Storchová Z
影响因子：
64.5
作者：
Davoli T;Xu AW;Mengwasser KE;Sack LM;Yoon JC;Park PJ;Elledge SJ
通讯作者：
Elledge SJ
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
64.8
作者：
Cohen-Sharir Y;McFarland JM;Abdusamad M;Marquis C;Bernhard SV;Kazachkova M;Tang H;Ippolito MR;Laue K;Zerbib J;Malaby HLH;Jones A;Stautmeister LM;Bockaj I;Wardenaar R;Lyons N;Nagaraja A;Bass AJ;Spierings DCJ;Foijer F;Beroukhim R;Santaguida S;Golub TR;Stumpff J;Storchová Z;Ben-David U
通讯作者：
Ben-David U
影响因子：
6.4
作者：
Duijf, Pascal H. G.;Schultz, Nikolaus;Benezra, Robert
通讯作者：
Benezra, Robert