Drosophila morgue and the intersection between protein ubiquitination and programmed cell death.
In Drosophila, cell survival decisions are mediated by the integrated functions of the Grim-Reaper death activators and Inhibitor-of-Apoptosis-Proteins (IAPs), such as DIAP1, to regulate caspase activities. We recently identified a gene that enhances the actions of the Grim-Reaper proteins and negatively regulates the levels of DIAP1 protein. This gene, morgue, encodes a novel protein that contains both an F box and a ubiquitin conjugase domain. Interestingly, the Morgue conjugase domain lacks the active site cysteine required for covalent linkage to ubiquitin. Morgue could target IAPs and other proteins for ubiquitination and proteasome-dependent turnover by acting either in an SCF ubiquitin E3 ligase complex, or as a ubiquitin E2 conjugase enzyme variant (UEV) in conjunction with a catalytically active E2 conjugase. Morgue is evolutionarily conserved, as a Morgue ortholog was identified from the mosquito, Anopheles gambiae. Elucidation of morgue function should provide novel insights into the mechanisms of ubiquitination and programmed cell death.
Schreader
Barbara A
BA
Biology Department, Program in Molecular and Cellular Biology, University of Massachusetts at Amherst, Amherst, MA 01003, USA.
Wang
Yiqin
Y
Nambu
John R
JR
D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000378:metabolism; D017209:Apoptosis; D001665:Binding Sites; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D003545:Cysteine / Q000737:chemistry; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D029721:Drosophila Proteins; D005136:Eye Proteins; D025801:Ubiquitin; C460739:morgue protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D020169:Caspases; D003545:Cysteine