ANAPC7

ANAPC7 functions as a component of the mitotic machinery, where genetic epistasis places it within the KIF18A-dependent pathway governing mitotic progression: co-depletion of ANAPC7 partially rescues the mitotic arrest caused by KIF18A loss, in direct opposition to ANAPC5, which exacerbates that arrest (PMID:39677807, PMID:40596695). Beyond this mitotic role, ANAPC7 has been captured in physical-interaction contexts that have not been resolved into a defined mechanism—it binds the cytoplasmic tails of IL-17RA and IL-17RC in a yeast two-hybrid screen, but its knockdown produces no detectable effect on IL-17 signaling (PMID:23922952). No catalytic activity, structural model, or substrate has been characterized for ANAPC7 in the available corpus.

1. 2013 Medium

   Testing whether ANAPC7 contributes to inflammatory receptor signaling, a yeast two-hybrid screen identified it as an IL-17 receptor binding partner, but functional knockdown showed it is dispensable for IL-17 signaling—placing its receptor association outside the IL-17 output pathway.

   Evidence Yeast two-hybrid screen with IL-17RA/IL-17RC cytoplasmic tails plus siRNA knockdown and IL-17-induced gene expression assays

   PMID:23922952

   Open questions at the time

   • The biological consequence of the ANAPC7–IL-17R interaction is unresolved given the negative knockdown result
   • No reciprocal validation or structural mapping of the interaction interface
   • Functional contrast with ANAPC5 (a negative regulator binding the same receptors) leaves ANAPC7's role unexplained
2. 2024 Medium

   To define ANAPC7's role in mitosis, genetic epistasis showed that depleting it partially relieves KIF18A-loss-induced mitotic arrest while depleting ANAPC5 worsens it, establishing the two subunits as functionally opposing within the KIF18A-dependent mitotic pathway.

   Evidence Double knockdown in cell lines and a mouse genetic screen comparing strain backgrounds, with quantitative expression analysis of an Anapc7 retroviral insertion

   PMID:39677807 PMID:40596695

   Open questions at the time

   • The molecular basis for opposing ANAPC5 and ANAPC7 effects within the same complex is not defined
   • Whether the rescue reflects altered APC/C substrate targeting is untested
   • No direct substrate or biochemical readout connects ANAPC7 to the KIF18A axis
3. 2024 Low

   Addressing how ANAPC7 expression is controlled, ChIP-seq showed C-FOS binds its promoter during mitotic clonal expansion in early adipogenesis, linking ANAPC7 transcription to an AP-1-driven proliferative program.

   Evidence ChIP-seq and expression analysis during mesenchymal stem cell adipogenesis

   PMID:38440920

   Open questions at the time

   • Promoter binding does not establish a functional regulatory consequence for ANAPC7
   • No knockdown or reporter assay confirms C-FOS-driven ANAPC7 transcription
   • Downstream effect of ANAPC7 levels on adipogenesis is uncharacterized
4. 2023 Low

   Probing a potential role in tumor immune evasion, co-immunoprecipitation identified ANAPC7 as a PD-L1 interactor in gastric cancer cells, with its expression linked to NK-cell-mediated immune escape.

   Evidence Co-immunoprecipitation and NK-92 co-culture assay in gastric cancer cells

   PMID:36592213

   Open questions at the time

   • Single Co-IP without reciprocal validation of the PD-L1 interaction
   • Mechanism connecting ANAPC7 to PD-L1 stability or function is not defined
   • Causal contribution of ANAPC7 to immune escape is not established beyond correlation

• The biochemical activity of ANAPC7 within its complex—how it engages substrates and how it produces effects opposite to ANAPC5—remains undefined.
• No substrate or catalytic activity identified for ANAPC7
• No structural model of how ANAPC7 and ANAPC5 contribute oppositely to mitotic progression
• Mechanistic link between physical partners (IL-17R, PD-L1) and ANAPC7's mitotic function is unexplored