PerspectiveCell Biology

The Proteome in Balance

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Science  13 Aug 2010:
Vol. 329, Issue 5993, pp. 766-767
DOI: 10.1126/science.1194160

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Inherited mutations and polymorphisms that alter the sequence of a polypeptide can affect its folding and stability, triggering disease at birth and during aging. A central cellular mechanism for generating and maintaining normal protein folds is the protein homeostasis or proteostasis network (referred to as the PN) (1). These processes sustain functional proteins as well as direct their removal from the cell during protein turnover or in response to misfolding. This “yin-yang” balance is critical for normal cellular, tissue, and organismal physiology. On page 805 in this issue, Okiyoneda et al. (2) show that the PN operates globally, constantly surveying protein folds, from co-translational insertion of proteins into the endoplasmic reticulum (ER) to removal of unstable proteins at the plasma membrane.