Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms.
Inhibitor of apoptosis (IAP) proteins suppress apoptosis and inhibit caspases. Several IAPs also function as ubiquitin-protein ligases. Regulators of IAP auto-ubiquitination, and thus IAP levels, have yet to be identified. Here we show that Head involution defective (Hid), Reaper (Rpr) and Grim downregulate Drosophila melanogaster IAP1 (DIAP) protein levels. Hid stimulates DIAP1 polyubiquitination and degradation. In contrast to Hid, Rpr and Grim can downregulate DIAP1 through mechanisms that do not require DIAP1 function as a ubiquitin-protein ligase. Observations with Grim suggest that one mechanism by which these proteins produce a relative decrease in DIAP1 levels is to promote a general suppression of protein translation. These observations define two mechanisms through which DIAP1 ubiquitination controls cell death: first, increased ubiquitination promotes degradation directly; second, a decrease in global protein synthesis results in a differential loss of short-lived proteins such as DIAP1. Because loss of DIAP1 is sufficient to promote caspase activation, these mechanisms should promote apoptosis.
Yoo
Soon Ji
SJ
Division of Biology, MC156-29, California Institute of Technology, Pasadena, CA 91125, USA.
Huh
Jun R
JR
Muro
Israel
I
Yu
Hong
H
Wang
Lijuan
L
Wang
Susan L
SL
Feldman
R M Renny
RM
Clem
Rollie J
RJ
Müller
H-Arno J
HA
Hay
Bruce A
BA
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins; D009479:Neuropeptides / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism
C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D009479:Neuropeptides; D010455:Peptides; D025801:Ubiquitin; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; D020169:Caspases; C118731:dronc protein, Drosophila