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Cellular ubiquitin pool dynamics and homeostasis

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Ubiquitin (Ub) is a versatile signaling molecule that playsimportant roles in a variety of cellular processes. Cellular Ubpools, which are composed of free Ub and Ub conjugates, arein dynamic equilibrium inside cells. In particular, increasingevidence suggests that Ub homeostasis, or the maintenance offree Ub above certain threshold levels, is important for cellularfunction and survival under normal or stress conditions. Accurate determination of various Ub species, including levelsof free Ub and specific Ub chain linkages, have becomepossible in biological specimens as a result of the introductionof the proteomic approach using mass spectrometry. Thistechnology has facilitated research on dynamic properties ofcellular Ub pools and has provided tools for in-depthinvestigation of Ub homeostasis. In this review, we have alsodiscussed the consequences of the disruption of Ub pooldynamics and homeostasis via deletion of polyubiquitin genesor mutations of deubiquitinating enzymes. The commonconsequence was a reduced availability of free Ub and asignificant impact on the function and viability of cells. Theseobservations further indicate that the levels of free Ub areimportant determinants for cellular protection.

Abstract

Ubiquitin (Ub) is a versatile signaling molecule that playsimportant roles in a variety of cellular processes. Cellular Ubpools, which are composed of free Ub and Ub conjugates, arein dynamic equilibrium inside cells. In particular, increasingevidence suggests that Ub homeostasis, or the maintenance offree Ub above certain threshold levels, is important for cellularfunction and survival under normal or stress conditions. Accurate determination of various Ub species, including levelsof free Ub and specific Ub chain linkages, have becomepossible in biological specimens as a result of the introductionof the proteomic approach using mass spectrometry. Thistechnology has facilitated research on dynamic properties ofcellular Ub pools and has provided tools for in-depthinvestigation of Ub homeostasis. In this review, we have alsodiscussed the consequences of the disruption of Ub pooldynamics and homeostasis via deletion of polyubiquitin genesor mutations of deubiquitinating enzymes. The commonconsequence was a reduced availability of free Ub and asignificant impact on the function and viability of cells. Theseobservations further indicate that the levels of free Ub areimportant determinants for cellular protection.

참고문헌 (57)

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