MOLECULAR CONTROL OF CELL GROWTH

University Of Washington, Seattle WA

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Linked publications & trials

Abstract

Size homeostasis is a property of both dividing and non-dividing cells. Proliferating cells double in size each mitotic cell cycle, so that daughter cells are neither bigger now smaller on average then their parents. Conversely, growth slows or stops when cells exit the division cycle and become quiescent or post-mitotic. Size homeostasis requires active coordination of growth with division. In actively proliferating cells, division would outstrip growth unless the chromosome cycle (DNA replication and mitosis) were constrained by a required (checkpoint) for adequate growth. Similarly exit from the cell cycle must be accompanied by pathways that not only stop the duplication of chromosomes but all other cellular constituents as well. In pathologic states of cellular hypertrophy, including kidney disease where cell hypertrophy is maladaptive, these processes are uncoupled so that cell growth continues under conditions were cell proliferation hs stopped. The molecular pathways that couple the chromosome cycle to cell growth are not understood. In this application we propose to explore these pathways and identify the molecular that link cell growth to cell proliferation. We will use this information to study how these pathways go awry in pathologic states of cellular hypertrophy and hyperplasia.