Table 2.
Screening of C. elegans mutants with sensitivity and resistance to edelfosine
| Strain (allele) | Human homolog | Gene function | n | % hatched (control)a | n | % hatched (10 μM)b | n | % hatched (20 μM)c | ratio 10 μM vs. control | ratio 20 μM vs. control |
|---|---|---|---|---|---|---|---|---|---|---|
| N2 wild type | - | - | 225 | 100.0 | 251 | 96.8 | 245 | 1.2 | 0.97 | 0.01 |
| N2 wild type | - | - | 244 | 98.8 | 281 | 93.2 | 358 | 0.8 | 0.94 | 0.01 |
| N2 wild type | - | - | 421 | 99.3 | 469 | 93.4 | 479 | 0.2 | 0.94 | 0.00 |
| N2 wild type | - | - | 587 | 100.0 | 651 | 91.2 | 611 | 2.6 | 0.91 | 0.03 |
| N2 wild type | - | - | 333 | 99.7 | 294 | 97.6 | 264 | 1.1 | 0.98 | 0.01 |
| N2 wild type | - | - | 296 | 99.3 | 292 | 94.5 | 290 | 0.0 | 0.95 | 0.00 |
| Cholesterol transport | ||||||||||
| rme-2(b1008) | LDL-like receptor | Nematode egg yolk uptake | 679 | 19.6 | 491 | 7.5 | 667 | 0.0 | 0.38 | 0.00 |
| cav-1(ok2089) | CAV1 | Caveolin-mediated endocytosis | 348 | 97.1 | 367 | 94.0 | 367 | 0.0 | 0.97 | 0.00 |
| cav-2(hc191) | CAV2 | Caveolin-mediated endocytosis | 396 | 99.5 | 270 | 97.8 | 413 | 0.0 | 0.98 | 0.00 |
| Longevity | ||||||||||
| daf-2(e1370) | IGF1R | Insulin-like pathway receptor | 172 | 100.0 | 279 | 97.1 | 107 | 30.8 | 0.97 | 0.31 |
| age-1(hx546) | PIK3CA | 1-phosphatidylinositol-3-kinase | 347 | 97.1 | 349 | 96.9 | 402 | 1.7 | 1.00 | 0.02 |
| daf-16(mu86) | FOXO | Insulin-like signaling pathway transcription factor | 360 | 98.6 | 405 | 95.8 | 396 | 0.2 | 0.97 | 0.00 |
| daf-18(e1375) | PTEN | Lipid phosphatase | 257 | 100.0 | 244 | 93.4 | 243 | 3.7 | 0.93 | 0.04 |
| akt-1(mg306) | AKT1 | Serine-threonine protein kinase | 127 | 96.9 | 145 | 97.9 | 338 | 4.4 | 1.01 | 0.05 |
| akt-2(tm812); sgk-1(ft15) | AKT2; SGK1 | Serine-threonine protein kinases | 267 | 98.5 | 173 | 98.3 | 262 | 1.2 | 1.00 | 0.01 |
| pdk-1(sa680) | PDK1 | Serine-threonine/tyrosine-protein kinase | 165 | 84.5 | 65 | 81.5 | 280 | 58.9 | 0.97 | 0.70 |
| clk-1(qm30) | COQ7 | Ubiquinone biosynthesis | 165 | 98.2 | 150 | 97.3 | 129 | 0.0 | 0.99 | 0.00 |
| isp-1(qm150) | UQCR5 | Ubiquinol-cytochrome C reductase | 158 | 90.5 | 127 | 74.0 | 134 | 0.0 | 0.82 | 0.00 |
| nuo-6(qm200) | MTND1 | NADH:ubiquinone oxidoreductase | 188 | 97.3 | 171 | 95.3 | 259 | 0.0 | 0.98 | 0.00 |
| eat-2(ad465) | nAChR | Pharyngeal pumping rate regulation | 293 | 98.9 | 270 | 59.3 | 371 | 0.3 | 0.60 | 0.00 |
| Proteins associated to lipid rafts | ||||||||||
| pho-1(ca101ca102) | ACPP | Phosphatase | 318 | 79.3 | 377 | 79.3 | 338 | 0.9 | 1.00 | 0.01 |
| tag-10(ok246) | MUC2 | Oligomeric gel-forming | 192 | 100.0 | 322 | 97.1 | 220 | 0.0 | 0.99 | 0.00 |
| gfi-1(ok2669) | FBN2 | Development | 295 | 98.3 | 337 | 95.6 | 322 | 0.0 | 0.97 | 0.00 |
| dod-19(ok2679) | GPR112 | G protein-coupled receptor | 159 | 96.9 | 213 | 85.0 | 232 | 0.0 | 0.88 | 0.00 |
| tre-3(ok394) | TREH | Trehalase activity | 144 | 100.0 | 158 | 84.8 | 305 | 0.0 | 0.85 | 0.00 |
| lec-1(ok1597) | Galectin | Sugar binding | 279 | 99.3 | 311 | 97.4 | 311 | 0.6 | 0.98 | 0.01 |
| daf-21(p673) | HSP90 | Heat shock protein | 211 | 98.6 | 245 | 99.2 | 203 | 29.6 | 1.01 | 0.30 |
| Sphingolipid biosynthesis | ||||||||||
| sptl-2(ok2753) | SPTLC2 | Serine Palmitoyl Transferase | 138 | 96.4 | 108 | 86.1 | 240 | 1.3 | 0.89 | 0.01 |
| sptl-3(ok1927) | SPTLC3 | Serine Palmitoyl Transferase | 319 | 98.8 | 286 | 94.1 | 292 | 0.3 | 0.95 | 0.00 |
| C23H3.4(ok1693) | SPTLC1 | Serine Palmitoyl Transferase | 280 | 98.2 | 337 | 92.6 | 395 | 0.5 | 0.94 | 0.01 |
| S. cerevisae deletion screening | ||||||||||
| tat-6(ok1984) | ATP9B | Aminophospholipid translocase | 263 | 85.6 | 218 | 80.3 | 320 | 0.0 | 0.94 | 0.00 |
| apc-10 and tag314(gk143) | ANAPC-10 | Fission yeast anaphase promoting complex | 663 | 14.9 | 640 | 13.8 | 766 | 4.7 | 0.92 | 0.31 |
| ZK370.3(ok1081) | HIP1R | Huntingtin interacting protein 1 related | 486 | 63.0 | 535 | 50.8 | 612 | 0.0 | 0.81 | 0.00 |
| ehs-1(ok146) | EPS15L1 | Calcium ion binding | 564 | 100.0 | 517 | 94.2 | 573 | 0.9 | 0.94 | 0.01 |
| hum-1(ok634) | MYO1E | ATP binding | 558 | 99.3 | 441 | 84.4 | 484 | 1.7 | 0.85 | 0.02 |
| Y65B4A.3(ok2425) | CHMP6 | Charged multivesicular body protein 6 | 347 | 70.0 | 427 | 62.3 | 430 | 2.1 | 0.89 | 0.03 |
| alx-1(gk338) | PDCD6IP | Notch binding | 429 | 98.1 | 445 | 98.2 | 369 | 2.7 | 1.00 | 0.03 |
| vps-35(ok1880) | VPS35 | Receptor-mediated endocytosis | 52 | 92.3 | 43 | 93.2 | 42 | 66.7 | 1.01 | 0.72 |
| vps-52(ok853) | VPS52 | Rab GTPase binding | 184 | 91.9 | 117 | 41.9 | 149 | 0.0 | 0.46 | 0.00 |
| max-2(ok1904) | PAK3 | Rac GTPase binding | 25 | 92.0 | 51 | 76.5 | 57 | 1.75 | 0.83 | 0.02 |
| tam-1(ok2635) | MLL2 | Larval development | 312 | 97.8 | 340 | 94.4 | 249 | 0.8 | 0.97 | 0.01 |
| F42G9.1(ok540) | PPM1G | Phosphatase | 85 | 76.5 | 102 | 77.5 | 76 | 0.0 | 1.01 | 0.00 |
| elo-6(gk233) | ELOVL3 | Regulation of growth rate | 576 | 98.4 | 620 | 94.7 | 515 | 2.1 | 0.96 | 0.02 |
| pld-1(ok2222) | PLD1 | Phospholipase D | 411 | 99.0 | 417 | 81.0 | 402 | 0.5 | 0.82 | 0.01 |
| T04C9.1a(ok1510) | ARHGAP42 | Rho GTPase activating protein 42 | 427 | 99.3 | 434 | 97.0 | 420 | 0.0 | 0.98 | 0.00 |
| vha-12(ok821) | ATP6-V1B2 | Proton-transporting ATPase | 188 | 97.3 | 121 | 95.9 | 287 | 0.4 | 0.98 | 0.00 |
| F54A3.4(ok666) | CBS | Cystathionine-beta-synthase | 314 | 98.7 | 326 | 95.4 | 270 | 0.0 | 0.97 | 0.00 |
| Apoptosis | ||||||||||
| egl-1(n487) | BH3 | Apoptosis activator | 255 | 99.2 | 209 | 99.0 | 365 | 59.7 | 1.00 | 0.60 |
| ced-9(n1950) | BCL2 | Apoptosis inhibitor | 284 | 78.9 | 294 | 80.6 | 255 | 0.0 | 1.02 | 0.00 |
| ced-4(n1162) | APAF1 | BH3 domain binding | 261 | 91.2 | 173 | 71.7 | 265 | 0.0 | 0.79 | 0.00 |
| ced-3(n717) | caspase 3/9 | Cysteine-aspartate protease | 329 | 96.4 | 288 | 78.1 | 375 | 0.0 | 0.81 | 0.00 |
| cps-6(ok1718) | EndoG | Mito-endonuclease G | 337 | 98.2 | 312 | 91.0 | 360 | 0.3 | 0.93 | 0.00 |
| Stress response | ||||||||||
| hif-1(ia4) | HIF1 | Hypoxia-induced factor | 411 | 99.5 | 467 | 93.4 | 486 | 0.0 | 0.94 | 0.00 |
| hsf-1(sy441) | HSF1 | Heat-shock transcription factor | 258 | 99.6 | 330 | 97.0 | 390 | 34.5 | 0.97 | 0.35 |
| jnk-1(gk7) | JNK1 | c-Jun N-terminal kinase | 370 | 100.0 | 374 | 97.3 | 405 | 0.0 | 0.97 | 0.00 |
| hsp-4(gk514) | HSP70 | Heat-shock response | 269 | 91.8 | 269 | 81.4 | 258 | 1.9 | 0.89 | 0.02 |
| hsp-16.2(gk249) | HSP16 | Heat-shock response | 278 | 100.0 | 265 | 98.1 | 285 | 0.0 | 0.98 | 0.00 |
| hsp-16.48(ok577) | HSP16 | Heat-shock response | 205 | 98.1 | 215 | 91.6 | 207 | 0.0 | 0.93 | 0.00 |
| hsp-43(ok647) | HSP-20 | Heat-shock response | 213 | 100.0 | 250 | 94.0 | 241 | 0.4 | 0.94 | 0.00 |
| hsp-12.6(ok1077) | HSP | Heat-shock response | 386 | 99.7 | 296 | 65.9 | 406 | 0.0 | 0.66 | 0.00 |
| hsp-3(ok1083) | HSP70 | Heat-shock response | 214 | 99.1 | 230 | 95.7 | 245 | 0.4 | 0.97 | 0.00 |
| hsp-12.3(ok3095) | HSP | Heat-shock response | 110 | 59.1 | 162 | 52.5 | 345 | 0.0 | 0.89 | 0.00 |
| hsp-12.2(ok3638) | HSP | Heat-shock response | 258 | 93.0 | 222 | 92.3 | 172 | 2.9 | 0.99 | 0.03 |
Highlighted in bold are the mutant strains that displayed resistance or sensitivity to edelfosine.
a
percentage of embryos that are able to hatch into larvae when maintained in control plates without edelfosine.
b
percentage of embryos that are able to hatch into larvae when maintained in plates containing 10 μM of edelfosine.
c
percentage of embryos that are able to hatch into larvae when maintained in plates containing 20 μM of edelfosine.