Temporal integration of mitogen history in mother cells controls proliferation of daughter cells

• Published in: Science (American Association for the Advancement of Science) Vol. 368; no. 6496; pp. 1261 - 1265
• Main Authors: Min, Mingwei, Rong, Yao, Tian, Chengzhe, Spencer, Sabrina L
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 12.06.2020
• Subjects: Availability; Cell cycle; Cell division; Cell growth; Cell Proliferation; Cyclin D - genetics; Cyclin D - metabolism; G1 Phase; G2 Phase; Growth factors; Humans; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogens; Mitogens - metabolism; Mothers; Protein Biosynthesis; Proteins; Signal processing; Signal Transduction; Signaling; Stem Cells - metabolism; Stem Cells - physiology; Translation
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aay8241

Multicellular organisms use mitogens to regulate cell proliferation, but how fluctuating mitogenic signals are converted into proliferation-quiescence decisions is poorly understood. In this work, we combined live-cell imaging with temporally controlled perturbations to determine the time scale and mechanisms underlying this system in human cells. Contrary to the textbook model that cells sense mitogen availability only in the G cell cycle phase, we find that mitogenic signaling is temporally integrated throughout the entire mother cell cycle and that even a 1-hour lapse in mitogen signaling can influence cell proliferation more than 12 hours later. Protein translation rates serve as the integrator that proportionally converts mitogen history into corresponding levels of cyclin D in the G phase of the mother cell, which controls the proliferation-quiescence decision in daughter cells and thereby couples protein production with cell proliferation.