| First Author | Baek HJ | Year | 2016 |
| Journal | Int J Biol Sci | Volume | 12 |
| Issue | 2 | Pages | 172-83 |
| PubMed ID | 26884715 | Mgi Jnum | J:309172 |
| Mgi Id | MGI:6755721 | Doi | 10.7150/ijbs.13420 |
| Citation | Baek HJ, et al. (2016) Caspase-3/7-mediated Cleavage of beta2-spectrin is Required for Acetaminophen-induced Liver Damage. Int J Biol Sci 12(2):172-83 |
| abstractText | UNLABELLED: The ubiquitously expressed beta2-spectrin (beta2SP, SPTBN1) is the most common non-erythrocytic member of the beta-spectrin gene family. Loss of beta2-spectrin leads to defects in liver development, and its haploinsufficiency spontaneously leads to chronic liver disease and the eventual development of hepatocellular cancer. However, the specific role of beta2-spectrin in liver homeostasis remains to be elucidated. Here, we reported that beta2-spectrin was cleaved by caspase-3/7 upon treatment with acetaminophen which is the main cause of acute liver injury. Blockage of beta2-spectrin cleavage robustly attenuated beta2-spectrin-specific functions, including regulation of the cell cycle, apoptosis, and transcription. Cleaved fragments of beta2-spectrin were physiologically active, and the N- and C-terminal fragments retained discrete interaction partners and activity in transcriptional regulation and apoptosis, respectively. Cleavage of beta2-spectrin facilitated the redistribution of the resulting fragments under conditions of liver damage induced by acetaminophen. In contrast, downregulation of beta2-spectrin led to resistance to acetaminophen-induced cytotoxicity, and its insufficiency in the liver promoted suppression of acetaminophen-induced liver damage and enhancement of liver regeneration. CONCLUSIONS: beta2-Spectrin, a TGF-beta mediator and signaling molecule, is cleaved and activated by caspase-3/7, consequently enhancing apoptosis and transcriptional control to determine cell fate upon liver damage. These findings have extended our knowledge on the spectrum of beta2-spectrin functions from a scaffolding protein to a target and transmitter of TGF-beta in liver damage. |
