Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer.

ABSTRACT: Almost all living cells maintain size uniformity through successive divisions. Proteins that over and underscale with size can act as rheostats, which regulate cell cycle progression. Using a multiomic strategy, we leveraged the heterogeneity of melanoma cell lines to identify peptides, transcripts, and phosphorylation events that differentially scale with cell size. Subscaling proteins are enriched in regulators of the DNA damage response and cell cycle progression, whereas super-scaling proteins included regulators of the cytoskeleton, extracellular matrix, and inflammatory response. Mathematical modeling suggested that decoupling growth and proliferative signaling may facilitate cell cycle entry over senescence in large cells when mitogenic signaling is decreased. Regression analysis re

SUBMITTER: Jones I 

PROVIDER: S-EPMC9876555 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature