Proteome complexity and the forces that drive proteome imbalance

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The cellular proteome is a complex microcosm of structural and regulatory networks that requires continuous surveillance and modification to meet the dynamic needs of the cell. It is therefore crucial that the protein flux of the cell remains in balance to ensure proper cell function. Genetic alterations that range from chromosome imbalance to oncogene activation can affect the speed, fidelity and capacity of protein biogenesis and degradation systems, which often results in proteome imbalance. An improved understanding of the causes and consequences of proteome imbalance is helping to reveal how these systems can be targeted to treat diseases such as cancer.

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Figure 1: An overview of proteome complexity.
Figure 2: Mechanisms that contribute to proteome imbalance and transcriptional responses.
Figure 3: Regulating the stoichiometry of protein complexes.
Figure 4: Therapeutic strategies that target proteome maintenance.


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J.W.H. is supported by grants from the US National Institutes of Health (AG011085, R37NS083524 and GM095567) and by grants from Biogen, Inc. E.J.B. is supported by grants from the National Institutes of Health (1DP2GM119132 and 2P50GM085764) and by a New Scholar in Aging award from The Ellison Medical Foundation (AG-NS-0902-12). We thank A. Amon at the Massachusetts Insitute of Technology for providing comments and insight during the preparation of this manuscript.

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Harper, J., Bennett, E. Proteome complexity and the forces that drive proteome imbalance. Nature 537, 328–338 (2016) doi:10.1038/nature19947

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