A state of partial Rb inactivation and intermediate E2F activation safeguards proliferation commitment

Dr. Yumi Konagaya (Ida)

Department of Cell & Developmental Biology, Weill Cornell Medicine, New York, NY, USA


     Many biological processes such as tissue repair, immune defense, and cancer progression rely on a vital cellular decision of whether to proliferate or stay in quiescence. Mammalian cells commit to proliferation by triggering a positive feedback whereby the transcription factor E2F activates cyclin-dependent kinase 2 (CDK2), which phosphorylates the E2F inhibitor retinoblastoma (Rb) leading to a further increase in E2F activity to express the genes necessary for proliferation. How cells manage to trigger the positive feedback only when needed is a fundamental question since positive feedbacks can inadvertently amplify small perturbations. We use single-cell analysis of E2F and CDK2 activity dynamics to determine how cells control the positive feedback to safeguard proliferation commitment. Strikingly, cells spend variable times of a few hours to over 20 hours in a reversible state of intermediate E2F activity. The intermediate E2F activity is proportional to the amount of phosphorylation of an evolutionary conserved Threonine 373 (T373) site in Rb. In this seminar, I will discuss a dedicated molecular state of intermediate E2F activation in which cells integrate fluctuating signals to reliably decide whether to disengage or fully engage the positive feedback that flips the Rb-E2F switch and initiates cell proliferation.

Date: Feb. 20, 2023 (Mon) 13:30 – 15:00
Place: Zoom and Room 412, Faculty of Science Building 3, University of Tokyo
Host: Shinya Kuroda

If you would like to attend, please email us at info.kuroda-lab [at] bs.s.u-tokyo.ac.jp and we will send you the Zoom URL. Please use your institution’s e-mail address and let us know your name and affiliation.