TEDC2

TEDC2 is a centrosomal protein that forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin, and this complex is essential for building and maintaining centriole triplet microtubule architecture (PMID:40067174). Within the complex, TEDC1 and TEDC2 form a subcomplex whose assembly requires the TEDC1 C-terminus, and centrosomal localization of TEDC2 is mutually dependent on TEDC1, delta-tubulin, and epsilon-tubulin (PMID:40067174, PMID:39979680). Loss of TEDC2 produces centrioles that lack triplet microtubules and central core scaffold proteins (e.g., POC5), exhibit an expanded proximal region, and undergo a futile cycle of elongation, fragmentation, and disintegration during mitosis (PMID:40067174). TEDC2 knockdown in non-small cell lung cancer cells inhibits Hedgehog signaling and reduces proliferation and cancer stem cell maintenance (PMID:41352505).

1. 2023 Low

   Initial cancer-cell studies raised the question of whether TEDC2 has a general role in cell proliferation, showing that its overexpression promotes proliferation and migration in hepatocellular carcinoma cells.

   Evidence Overexpression and proliferation/migration assays in HCC cell lines

   PMID:37867019

   Open questions at the time

   • Single-lab overexpression study without mechanistic pathway identification
   • TP53–TEDC2 regulatory link is bioinformatic only, not validated experimentally
   • No biochemical or structural understanding of TEDC2 function
2. 2024 Low

   Knockdown studies in lung adenocarcinoma cells corroborated that TEDC2 depletion impairs proliferation and migration, but still without identifying the underlying mechanism.

   Evidence siRNA knockdown with CCK8 proliferation and transwell assays in LUAD lines

   PMID:39553728

   Open questions at the time

   • No pathway mechanism identified
   • Not independently confirmed outside a single lab
   • No connection to centriole biology yet established
3. 2025 High

   The core biochemical identity of TEDC2 was established: it forms a tetrameric complex with TEDC1, delta-tubulin, and epsilon-tubulin that localizes to centrosomes and is required for centriole triplet microtubule architecture, with loss causing centriole structural collapse and mitotic fragmentation.

   Evidence Reciprocal co-immunoprecipitation, CRISPR/Cas9 knockout in human cells, ultrastructure expansion microscopy, AlphaFold Multimer modeling

   PMID:40067174

   Open questions at the time

   • How the tetramer is recruited to the centriole and at what stage of centriole biogenesis it acts is unresolved
   • Stoichiometry and atomic-resolution structure of the endogenous complex have not been determined experimentally
   • Whether loss of triplet microtubules explains the proliferation defects seen in cancer knockdown studies is untested
4. 2025 Medium

   The TEDC1–TEDC2 interaction interface was defined: a patient-derived TEDC1 C-terminal truncation disrupts binding to TEDC2, demonstrating that the TEDC1 C-terminus is required for subcomplex formation.

   Evidence Patient exome sequencing, in vitro binding assay with truncated TEDC1

   PMID:39979680

   Open questions at the time

   • Whether this variant causes a Mendelian ciliopathy phenotype in patients has not been firmly established
   • Residue-level mapping of the TEDC1–TEDC2 binding interface is lacking
5. 2025 Medium

   A signaling pathway was linked to TEDC2's proliferative role: TEDC2 knockdown in NSCLC cells inhibited Hedgehog signaling, reduced cancer stem cell maintenance, and sensitized cells to cisplatin.

   Evidence siRNA/shRNA knockdown, Hedgehog pathway reporter assays, in vivo xenograft

   PMID:41352505

   Open questions at the time

   • Whether the Hedgehog link is a direct consequence of defective centriole/cilium architecture or an independent function is unknown
   • No direct biochemical interaction between TEDC2 and Hedgehog pathway components has been shown

• Key open questions include how the TEDC1–TEDC2–delta-tubulin–epsilon-tubulin tetramer is recruited to nascent centrioles, whether TEDC2 loss causes ciliopathy in humans, and whether the cancer-cell phenotypes are secondary to centriole/cilium defects.
• No experimental structure of the endogenous tetramer at atomic resolution
• Mechanism linking centriole triplet microtubule loss to Hedgehog pathway suppression is unknown
• In vivo organismal phenotype of TEDC2 loss in mammals has not been reported