第1435回生物科学セミナー

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

Yumi Konagaya (Ida) 博士(Department of Cell & Developmental Biology, Weill Cornell Medicine, New York, NY, USA)

2023年02月20日(月)    13:30-15:00  理学部3号館412号室及びZoom   

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.

*授業成績には反映されません。

学外で参加希望のかたは、info.kuroda-lab@bs.s.u-tokyo.ac.jpまでメールをいただければ、ZoomのURLを送付いたします。所属機関のメールアドレスでお願いいたします。個人のメールアドレスはお控えください。その際には、氏名と所属も合わせてお願いいたします。

担当: 理学系研究科 生物科学専攻 生物情報科学科 黒田研究室  黒田 真也