| First Author | Yosefzon Y | Year | 2018 |
| Journal | Mol Cell | Volume | 70 |
| Issue | 4 | Pages | 573-587.e4 |
| PubMed ID | 29775577 | Mgi Jnum | J:262398 |
| Mgi Id | MGI:6159315 | Doi | 10.1016/j.molcel.2018.04.019 |
| Citation | Yosefzon Y, et al. (2018) Caspase-3 Regulates YAP-Dependent Cell Proliferation and Organ Size. Mol Cell 70(4):573-587.e4 |
| abstractText | 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 alpha-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. |
