Quantitative proteomic analysis of Myc oncoprotein function

被引:153
作者
Shiio, Y
Donohoe, S
Yi, EC
Goodlett, DR
Aebersold, R
Eisenman, RN
机构
[1] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA
[2] Inst Syst Biol, Seattle, WA 98103 USA
关键词
cell growth; cytoskeleton; CAT (TM) reagent; Myc oncoprotein; proteomics;
D O I
10.1093/emboj/cdf525
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study applies a new quantitative proteomics technology to the analysis of the function of the Myc oncoprotein in mammalian cells. Employing isotope-coded affinity tag (ICAT(TM)) reagent labeling and tandem mass spectrometry, the global pattern of protein expression in rat myc-null cells was compared with that of myc-plus cells (myc-null cells in which myc has been introduced) to generate a differential protein expression catalog. Expression differences among many functionally related proteins were identified, including reduction of proteases, induction of protein synthesis pathways and upregulation of anabolic enzymes in myc-plus cells, which are predicted to lead to increased cell mass (cell growth). In addition, reduction in the levels of adhesion molecules, actin network proteins and Rho pathway proteins were observed in myc-plus cells, leading to reduced focal adhesions and actin stress fibers as well as altered morphology. These effects are dependent on the highly conserved Myc Box II region. Our results reveal a novel cytoskeletal function for Myc and indicate the feasibility of quantitative whole-proteome analysis in mammalian cells.
引用
收藏
页码:5088 / 5096
页数:9
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