CCDC116

CCDC116 is a centrosome-associated protein that functions as a downstream effector promoting centriole overduplication (PMID:25074808, PMID:41401801). It is recruited to the centrosome through a PLK1–CEP20 signaling axis: PLK1-dependent phosphorylation of CEP20 at Ser46 generates a high-affinity binding site for CCDC116, and a phospho-deficient CEP20-S46A mutant fails to support this recruitment (PMID:41401801). Knockdown of CCDC116 abolishes centrosomal localization of the CEP20–CCDC116 complex and prevents centrosome amplification, including the overduplication driven by Nε-carboxymethyl-lysine (CML) exposure in human hepatocytes, establishing CCDC116 as a required effector for centriole overduplication in this pathway (PMID:41401801). Beyond its recruitment by phospho-CEP20 and its requirement for centrosome amplification, no biochemical activity or structural detail for CCDC116 has been characterized in the available corpus.

1. 2014 Medium

   Established CCDC116 as a centrosome-associated protein, placing an otherwise uncharacterized protein at a defined subcellular structure and motivating a centriole-related function.

   Evidence Mass spectrometry of sperm centrioles with immunofluorescence localization in cultured mammalian cells

   PMID:25074808

   Open questions at the time

   • Single localization experiment with no functional follow-up
   • No interacting partners or recruitment mechanism identified
   • No molecular activity assigned
2. 2025 Medium

   Defined how CCDC116 reaches the centrosome and what it does there, showing PLK1-phosphorylated CEP20 (phospho-Ser46) recruits CCDC116 to drive centriole overduplication.

   Evidence CEP20-S46A phospho-mutant and CCDC116 knockdown with centrosome amplification quantification in human hepatocytes (THLE2/THLE3)

   PMID:41401801

   Open questions at the time

   • Direct CCDC116–CEP20 binding affinity and stoichiometry not structurally resolved
   • Biochemical activity of CCDC116 itself unknown
   • Findings from a single lab
3. 2025 Medium

   Showed CCDC116 is a required downstream effector by demonstrating its loss blocks CML-induced centrosome amplification, linking the recruitment axis to a defined upstream stimulus.

   Evidence siRNA/shRNA knockdown of CCDC116 in human hepatocytes with centrosome amplification assay under CML treatment

   PMID:41401801

   Open questions at the time

   • Molecular mechanism by which CCDC116 promotes overduplication is undefined
   • Whether the requirement generalizes beyond the CML/hepatocyte context is untested
   • No reciprocal validation of complex composition in an independent system

• The intrinsic biochemical activity of CCDC116 and how its centrosomal recruitment mechanistically triggers centriole overduplication remain unresolved.
• No enzymatic or structural function assigned to CCDC116
• Downstream effectors engaged by centrosomal CCDC116 unknown
• No structural model of the phospho-CEP20–CCDC116 interface