Abstract
Apoptosis culminates in the activation of caspase-3, which plays an important role in implementing the cell death program. Here, we reveal a non-apoptotic role of caspase-3 as a key regulator of cell proliferation and organ size. Caspase-3 is specifically activated in the proliferating cells of the sebaceous gland, but does not instruct cell elimination. Deletion or chemical inhibition of caspase-3 diminishes cell proliferation, decreases cell number and reduces sebaceous gland size in vivo. Exploring the underlying mechanism, we demonstrate that α-catenin is cleaved by caspase-3, thus facilitating the activation and nuclear translocation of yes-associated protein (YAP), a vital regulator of organ size. Accordingly, activation of caspase-3 leads to YAP-dependent organ size augmentation. Finally, we show that X-linked inhibitor of apoptosis protein (XIAP) serves as an endogenous feedback antagonist for the caspase-3/YAP signaling module. Taken together, we report here a molecular mechanism wherein the apoptotic machinery is refocused to regulate cell proliferation and orchestrate organ size.
Citations
May 6, 2019·The British Journal of Dermatology·R W ClaytonX Lim
Jan 24, 2020·Biological Reviews of the Cambridge Philosophical Society·Richard W ClaytonRalf Paus
Mar 12, 2020·Stem Cells·Mingyu XiaWenyan Li
Mar 9, 2019·Science·Yaron Fuchs
May 30, 2019·Nature Communications·Alona FeldmanYaron Fuchs
May 7, 2019·Cells·Emanuel Rognoni, Gernot Walko
Sep 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Natsuki ShinodaMasayuki Miura
Sep 27, 2018·Molecular & Cellular Oncology·Yahav Yosefzon, Yaron Fuchs
Oct 22, 2020·Mediators of Inflammation·Peng SunFeng Zhou
Nov 13, 2020·The FEBS Journal·Camila Castillo FerrerGabriel Ichim
Oct 16, 2019·Cancer Research·Antoine BernardRomain Boidot
Jan 20, 2021·Cancer Discovery·Elle Koren, Yaron Fuchs
Jul 1, 2020·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Nir Shahar, Sarit Larisch
Nov 6, 2018·Developmental Biology·Amalia RosnerBaruch Rinkevich
May 29, 2021·Neurochemistry International·Eylem BaysalN Dilara Zeybek
Jun 8, 2021·Frontiers in Genetics·Feitong ShiYin Wang
Nov 16, 2020·Current Opinion in Cell Biology·Jessica Evangeline Tan Kabigting, Yusuke Toyama
Jul 2, 2021·Developmental Cell·Roi AnkawaYaron Fuchs
Jul 2, 2019·ACS Chemical Biology·Matthew W BoudreauPaul J Hergenrother
Apr 3, 2020·Biochimica Et Biophysica Acta. Biomembranes·Lorenza González-MariscalElida Amaya