| Substrate/target | Evidence type | Ubiquitin linkage (K48/K63/unspecified) | Modified residue(s) if known | Biological consequence | Key citation (with year, DOI URL) |
|---|---|---|---|---|---|
| p53 (phospho-p53 S315) | Interaction with phospho-p53, polyubiquitination assay, proteasomal degradation studies | Unspecified in primary snippet; summarized as K48-linked in later review table | p53 K291, K292; interaction depends on p53 S315 phosphorylation | FBXL6 promotes p53 degradation, relieving tumor-suppressive signaling and promoting tumor growth | Li et al., 2021, https://doi.org/10.1038/s41418-021-00739-6 (pqac-00000007, pqac-00000006) |
| HSP90AA1 | IP/MS identification, co-immunoprecipitation, in vivo ubiquitination assay, HCC functional assays | K63 | Not specified in gathered snippets | Stabilizes HSP90AA1, thereby sustaining c-MYC activity and promoting HCC growth | Shi et al., 2020, https://doi.org/10.1186/s12964-020-00604-y (pqac-00000008) |
| KRAS / KRASG12D | Co-IP, ubiquitination assay, RAS activity assay, transgenic mouse models, patient correlation analyses | Unspecified in primary snippet; summarized as K63-linked in later review table | KRAS K128 | Activates KRAS signaling, increases RAF binding and MEK/ERK/mTOR/PRELID2/ROS signaling, promoting HCC tumorigenesis and lung metastasis | Xiong et al., 2023, https://doi.org/10.1186/s40779-023-00501-8 (pqac-00000009, pqac-00000014, pqac-00000006) |
| TKT (transketolase) | Mass-spectrometry candidate identification, co-IP, FBXL6 overexpression ubiquitination assay, F-box deletion mutant test, knockdown/inhibition rescue in vitro and in vivo | Unspecified | Recruitment requires TKT Thr287 phosphorylation by VRK2; ubiquitinated lysine(s) not specified | Activates TKT and downstream ROS-mTOR signaling, increasing PD-L1/VRK2, immune evasion, and HCC metastasis | Zhang et al., 2023, https://doi.org/10.1038/s12276-023-01060-7 (pqac-00000011, pqac-00000012, pqac-00000013) |
| CCNA2 (cyclin A2) | Interaction validation among five substrates; in vivo ubiquitination assay; protein half-life analysis | Unspecified | Not specified | FBXL6-mediated ubiquitination shortens CCNA2 half-life and reduces CCNA2 expression | Chen et al., 2019, https://doi.org/10.1016/j.isci.2019.05.033 (pqac-00000010) |
| VDAC2 | Interaction/ubiquitination assays with HA-Ub and FBXL6 knockdown context | Unspecified | Not specified | FBXL6-associated ubiquitination correlates with reduced VDAC2 expression | Chen et al., 2019, https://doi.org/10.1016/j.isci.2019.05.033 (pqac-00000010) |
| CDK4 | Validated interaction/co-purification in substrate network study | Unspecified | Not specified | Experimental interaction supported, but functional consequence not defined in gathered snippets | Chen et al., 2019, https://doi.org/10.1016/j.isci.2019.05.033 (pqac-00000010) |
| HSPD1 | Validated interaction/co-purification in substrate network study | Unspecified | Not specified | Experimental interaction supported, but functional consequence not defined in gathered snippets | Chen et al., 2019, https://doi.org/10.1016/j.isci.2019.05.033 (pqac-00000010) |
| ETV6 (TEL) | Prior report cited in gathered snippets as ubiquitin-proteasome substrate of FBXL6 | Unspecified | Not specified | FBXL6 promotes ETV6 degradation via the ubiquitin-proteasome system | Reported in Li et al., 2021 background discussion, https://doi.org/10.1038/s41418-021-00739-6 (pqac-00000007, pqac-00000009) |


*Table: This table summarizes experimentally supported human FBXL6 substrates or interactors, the types of evidence used to support each assignment, and the reported functional consequences. It is useful for distinguishing direct mechanistic evidence from broader association studies and for tracking which ubiquitin linkages or modified residues have actually been reported.*