CCDC102B

CCDC102B is a centrosome linker protein required for centrosome cohesion during interphase (PMID:30404835). It is recruited to the centrosome by C-Nap1 (CEP250) and interacts with the centrosome linker components rootletin and LRRC45, decorating and facilitating the formation of rootletin filaments; Nek2A-mediated phosphorylation drives its dissociation from the centrosome at the onset of mitosis (PMID:30404835). Independently, CCDC102B promotes breast cancer metastasis by activating the NF-κB pathway: it physically interacts with RACK1 and reduces the RACK1–IKKα association to potentiate NF-κB activation, while RACK1 in turn targets CCDC102B for lysosomal degradation through chaperone-mediated autophagy (PMID:35957886).

1. 2018 High

   Established CCDC102B as a bona fide centrosome linker protein and placed it within the C-Nap1/rootletin cohesion machinery and the Nek2A mitotic disengagement switch, defining its interphase cellular role.

   Evidence Co-IP, immunofluorescence localization, in vitro interaction and phosphorylation assays, and loss-of-function with a centrosome cohesion phenotype readout in cultured cells

   PMID:30404835

   Open questions at the time

   • Structural basis of CCDC102B binding to rootletin/LRRC45 not resolved
   • Specific Nek2A phosphosite(s) and their direct role in displacement not mapped
   • Whether CCDC102B is required for rootletin filament nucleation versus stabilization not distinguished
2. 2022 Medium

   Connected CCDC102B to cancer cell behavior by showing it activates NF-κB through RACK1/IKKα modulation and is reciprocally controlled by RACK1-driven chaperone-mediated autophagy, linking its protein stability to a metastatic signaling output.

   Evidence Reciprocal Co-IP with mass spectrometry, CRISPR/Cas9 in vivo screening, RNA-seq, migration/invasion assays, and tail-vein and xenograft mouse models

   PMID:35957886

   Open questions at the time

   • Single-lab study; reciprocal validation of the NF-κB axis in independent models pending
   • Mechanistic link, if any, between the centrosome cohesion role and NF-κB/metastasis function unknown
   • CMA targeting motif on CCDC102B not defined

• Whether CCDC102B's centrosome-linker function and its RACK1/NF-κB metastatic function are mechanistically coupled remains unresolved.
• No experiment tests whether centrosome localization influences NF-κB signaling
• No structural or domain-level dissection separating the two activities