| First Author | Zettl M | Year | 2011 |
| Journal | Cell | Volume | 145 |
| Issue | 1 | Pages | 79-91 |
| PubMed ID | 21439629 | Mgi Jnum | J:173119 |
| Mgi Id | MGI:5009752 | Doi | 10.1016/j.cell.2011.02.047 |
| Citation | Zettl M, et al. (2011) Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell 145(1):79-91 |
| abstractText | Intramembrane proteolysis governs many cellular control processes, but little is known about how intramembrane proteases are regulated. iRhoms are a conserved subfamily of proteins related to rhomboid intramembrane serine proteases that lack key catalytic residues. We have used a combination of genetics and cell biology to determine that these 'pseudoproteases' inhibit rhomboid-dependent signaling by the epidermal growth factor receptor pathway in Drosophila, thereby regulating sleep. iRhoms prevent the cleavage of potential rhomboid substrates by promoting their destabilization by endoplasmic reticulum (ER)-associated degradation; this mechanism has been conserved in mammalian cells. The exploitation of the intrinsic quality control machinery of the ER represents a new mode of regulation of intercellular signaling. Inactive cognates of enzymes are common, but their functions are mostly unclear; our data indicate that pseudoenzymes can readily evolve into regulatory proteins, suggesting that this may be a significant evolutionary mechanism. |
