Zhe Jiang, Huiqin Li, Stephanie A Schroer, Veronique Voisin, YoungJun Ju, Marek Pacal, Natalie Erdmann, Wei Shi, Philip E D Chung, Tao Deng, Nien-Jung Chen, Giovanni Ciavarra, Alessandro Datti, Tak W Mak, Lea Harrington, Frederick A Dick, Gary D Bader, Rod Bremner, Minna Woo, Eldad Zacksenhaus
Despite extensive analysis of pRB phosphorylation in vitro, how this modification influences development and homeostasis in vivo is unclear. Here, we show that homozygous Rb∆K4 and Rb∆K7 knock-in mice, in which either four or all seven phosphorylation sites in the C-terminal region of pRb, respectively, have been abolished by Ser/Thr-to-Ala substitutions, undergo normal embryogenesis and early development, notwithstanding suppressed phosphorylation of additional upstream sites. Whereas Rb∆K4 mice exhibit telomere attrition but no other abnormalities, Rb∆K7 mice are smaller and display additional hallmarks of premature aging including infertility, kyphosis, and diabetes, indicating an accumulative effect of blocking pRb phosphorylation...
January 13, 2022: EMBO Journal