In Drosophila cells, the initiator caspase Dronc is kept inactive by the inhibitor of apoptosis protein Diap1, an E3 ubiquitin ligase that binds and ubiquitylates Dronc and effector caspases. Apoptotic stimuli induce the RHG proteins Reaper (Rpr), Head involution defective (Hid), Grim and Sickle (Skl), which share an N-terminal IAP-binding motif. They bind Diap1, displace the caspases and promote Diap1 degradation. Freed Dronc is recruited by the adaptor Dark into the apoptosome, a wheel-shaped complex in which Dronc is activated and then cleaves the effector caspases drICE and Dcp-1. The mitochondrial serine protease HtrA2 (Omi) also binds IAPs and can promote cell death.
Diap1 is not a member of the FlyBase APOP or RHG groups; it is added as a non-member gene because the RHG proteins act by antagonizing it. Effector caspases (Drice, Dcp-1) are downstream and are covered by apoptosis execution modules, not this one. Prx4 is kept because FlyBase places it in the RHG group, but its role as an IAP antagonist is not described here and should be checked. The upstream transcriptional induction of rpr, hid and grim (for example by p53 or ecdysone) is context. FlyBase groups realized by this module: APOP (FBgg0000129), RHG (FBgg0000177). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_rhg_apoptosome_caspase_activation.yaml. Member genes with a gene review in this repository: Dark, Diap1, Dronc, grim, hid, HtrA2, Prx4, rpr, skl.
All recommended fields populated.
✗ none found
No MODULE:dmel_rhg_apoptosome_caspase_activation deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
3 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (3 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| diap1_diap1 | Diap1 UniProtKB:Q24306 Gene |
ubiquitin protein ligase activity GO:0061630 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dark_apoptosome_complex/dark | Dark UniProtKB:Q7KLI1 Complex Unit |
cysteine-type endopeptidase activator activity GO:0140608 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dark_apoptosome_complex/dronc | Dronc UniProtKB:Q9XYF4 Complex Unit |
cysteine-type endopeptidase activity GO:0004197 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
✓ every negative regulator described as feedback has an upstream edge closing the loop.
2 complete review(s) · 9 with deep research · 0 missing review · 0 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| Dark Q7KLI1 | ✓ | 33/36 | ✓ |
| Diap1 Q24306 | ✓ | 74/102 | ✓ |
| Dronc Q9XYF4 | ✓ | 58/70 | ✓ |
| grim Q24570 | ✓ | 17/23 | ✓ |
| hid Q24106 | ✓ | 46/58 | ✓ |
| HtrA2 Q9VFJ3 | ✓ | ✓ | ✓ |
| Prx4 Q9V3Q4 | ✓ | ✓ | ✓ |
| rpr Q24475 | ✓ | 35/43 | ✓ |
| skl Q9VVP8 | ✓ | 9/11 | ✓ |
RHG IAP antagonists release Dronc from Diap1 inhibition so that the Dark apoptosome can activate it.
HtrA2, a mitochondrial serine protease with an IAP-binding motif, and Prx4, which FlyBase includes in the RHG group.