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
【概要】
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.
日時： 2023年2月20日（月） 13:30～15:00
場所： Zoom と 会場（東京大学、理学部3号館、412号室）
連絡先： 理学系研究科 生物科学専攻 生物情報科学科
黒田 真也（skuroda AT bs.s.u-tokyo.ac.jp）
参加希望の方は
info.kuroda-lab [at] bs.s.u-tokyo.ac.jp
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