Table 4.
Cellular proteins that bind PS ASOs
| A. PS ASO binding proteins localized to plasma membranes | ||
|---|---|---|
| Protein | Effects on ASO activity | Ref. |
| ASGPR | Enhance | (224) |
| EGFR | Enhance | (121) |
| LDLR | N/D | S. Wanget al., unpublished |
| M6PR | Enhance | (164) |
| TLRs | (mediate inflammatory effects) | (225) |
| Stabilin | Enhance | (226) |
| SRB | N/D | S. Wang et al., unpublished |
| Nucleolin | N/D | (227) |
| B. Cellular PS-ASO binding proteins | ||||||
|---|---|---|---|---|---|---|
| Protein | Feature | ASO activity upon protein knockdown | ASO localization | Impact on ASO toxicity | ASO-protein colocalization | References |
| Nucleic acid binding proteins (33) | ||||||
| Ago2 | RNA Binding | Reduced (free uptake) | Not characterized | Yes (P-bodies) | (228) | |
| CArG binding factor | RNA binding | Not characterized | Not characterized | (53) | ||
| DDX21 | RNA binding | Yes | Yes | Yes (toxic ASO) | L. Zhang et al., unpublished | |
| DHX30 | RNA binding | No change | No change | (53) | ||
| EIF2S2 | RNA binding | Not characterized | Not characterized | |||
| eIF4H | RNA binding | No change | No change | |||
| GRSF | RNA binding | No change | No change | |||
| HMGB1 | DNA binding | No change | No change | No | ||
| hnRNP D1Like | RNA binding | Not characterized | Not characterized | |||
| hnRNPA1 | RNA binding | Not characterized | Not characterized | (229) | ||
| hnRNPA2 | RNA binding | Not characterized | Not characterized | (53) | ||
| hnRNPF | RNA binding | Not characterized | Not characterized | |||
| hnRNPH1 | RNA binding | Not characterized | Not characterized | |||
| hnRNPK | RNA binding | Increase | Yes | Yes | (123) | |
| hnRNPQ | RNA binding | No change | No change | (53) | ||
| hnRNPU | RNA binding | Not characterized | Not characterized | |||
| hnRNPUL | RNA binding | Not characterized | Not characterized | |||
| ILF2 | RNA binding | Not characterized | Not characterized | |||
| ILF3 | RNA binding | No change | No change | |||
| KHSRP | RNA binding | No change | No change | |||
| Ku70 | DNA binding | Increase | No change | No | ||
| Ku80 | DNA binding | Increase | No change | No | ||
| La/SSB | RNA binding | Reduce | Yes | No | ||
| NCL | RNA binding | No change | No change | Yes (toxic ASO) | (230) | |
| NPM1 | RNA binding | Reduce | Yes | Yes (toxic ASO) | (53) | |
| P54nrb | RNA/DNA binding | Increase | Yes | Yes | Yes | (123) |
| PC4/Sub1 | DNA binding | Reduce | No change | No | (53) | |
| PSF | RNA/DNA binding | Increase | Yes | Yes | Yes | (123) |
| PSPC1 | RNA binding | Increase | Yes | Yes | (53) | |
| RHA | RNA binding | No change | No change | |||
| RNase H1 | DNA/RNA duplex binding | Reduce | No change | Yes | ||
| RNF163/ZNF9 | DNA binding | No change | No change | |||
| YBX1 protein | RNA binding | No change | Not characterized | Yes | ||
| Chaperone proteins (11) | ||||||
| GRP78/Bip | Chaperone protein | No change | No change | (53) | ||
| HSC70 | Chaperone protein | Reduce | No change | No | X.H. Liang et al., unpublished | |
| HSP90-AA1 | Chaperone protein | Reduce | No change | Yes | No | (54) |
| Hsp90-AB | Chaperone protein | Reduce | No change | Yes | ||
| HSPA1L | Chaperone protein | Not characterized | Not characterized | (53) | ||
| TCP1-alpha | Chaperone protein | Reduce | Not characterized | Yes (LE) | (114) | |
| TCP1-beta | Chaperone protein | Reduce | Not characterized | Yes (PS-body, LE) | ||
| TCP1-delta | Chaperone protein | Not characterized | Not characterized | Yes (LE) | ||
| TCP1-episilon | Chaperone protein | Reduce | Not characterized | Yes (LE) | ||
| TCP1-gamma | Chaperone protein | Not characterized | Not characterized | Yes (LE) | ||
| TCP1-Theta | Chaperone protein | Not characterized | Not characterized | Yes (LE) | ||
| Other proteins (17) | ||||||
| ACLY | Enzyme | No change | No change | (53) | ||
| Albumin | Secreted | Not characterized | Not characterized | (84) | ||
| Annexin A2 | Membrane binding | Reduce | Yes | Yes (LE) | (231) | |
| ATAD3A | Membrane | No change | No change | |||
| FTCD/58K | Enzyme | Reduce | Yes | Yes (LE) | X.H. Liang et al., unpublished | |
| IMP9 | Transport | Reduce | Yes | |||
| JKTPB1 delta 6 | hnNRP-like | Not characterized | Not characterized | (53) | ||
| KCTD12 | Membrane receptor | No change | No change | |||
| LRPPRC | Transport/transcription | No change | No change | |||
| NARS | tRNA synthase | No change | No change | |||
| NDKA | Enzyme | Not characterized | Not characterized | |||
| RAN | Transport | Reduce | Yes | |||
| SHMT2 | Enzyme | Not characterized | Not characterized | |||
| Thymidylate kinase | Enzyme | Not characterized | Not characterized | |||
| VARS | tRNA synthase | Reduce | No change | |||
| β-actin (ACTB) | Structure | Reduce | Not characterized | |||
| β-tubulin (TUBB2C) | Structure | No change | Not characterized | |||
Adapted from ref (38).
Bolded proteins demonstrated to influence ASO activity or localization.