期刊
CELL
卷 145, 期 1, 页码 79-91出版社
CELL PRESS
DOI: 10.1016/j.cell.2011.02.047
关键词
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资金
- Austrian FWF
- Austrian Academy of Science
- International Human Frontier Science Program Organization
- EMBO Long-Term Fellowship
- Marie Curie Intraeuropean Fellowship
- Medical Research Council [MC_U105178780] Funding Source: researchfish
- MRC [MC_U105178780] Funding Source: UKRI
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.
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