WDR23

WDR23 also known as Dcaf11 (Ddb1- and Cul4-associated factor 11) is a WD40 repeat protein, containing seven repeats of the closed circular solenoid protein domain WD40.[1] The WDR23 locus is highly conserved from C. elegans to humans.[2] DCAF11/WDR23 is the E3 ligase that specifically targets proteins for degradation via ubiquitination.[3][4][5] WDR-23 exists in two spatially distinct isoforms produced by alternative splicing, a cytoplasmic WDR-23A and nuclear WDR-23B. Nuclear and cytoplasmic versions of WDR-23 have distinct roles.[6]

References
  1. Choe, K. P., Przybysz, A. J., & Strange, K. (2009). The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. Molecular and cellular biology, 29(10), 2704-2715. PMID 19273594 PMC 2682033 doi:10.1128/MCB.01811-08
  2. Tang, L., & Choe, K. P. (2015). Characterization of skn-1/wdr-23 phenotypes in Caenorhabditis elegans; pleiotrophy, aging, glutathione, and interactions with other longevity pathways. Mechanisms of ageing and development, 149, 88-98. PMID 26056713 doi:10.1016/j.mad.2015.06.001
  3. Siswanto, F. M., Oguro, A., & Imaoka, S. (2021). Sp1 is a substrate of Keap1 and regulates the activity of CRL4AWDR23 ubiquitin ligase toward Nrf2. Journal of Biological Chemistry, 296. PMID 33895141 PMC 8141886 doi:10.1016/j.jbc.2021.100704
  4. Chen, Z., Wang, K., Hou, C., Jiang, K., Chen, B., Chen, J., ... & Shen, H. (2017). CRL4B DCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells. Scientific reports, 7(1), 1-12. PMID 28446751 PMC 5430835 doi:10.1038/s41598-017-01344-9
  5. Lo, J. Y., Spatola, B. N., & Curran, S. P. (2017). WDR23 regulates NRF2 independently of KEAP1. PLoS genetics, 13(4), e1006762. PMID 28453520 PMC 5428976 doi:10.1371/journal.pgen.1006762
  6. Spatola, B. N., Lo, J. Y., Wang, B., & Curran, S. P. (2019). Nuclear and cytoplasmic WDR-23 isoforms mediate differential effects on GEN-1 and SKN-1 substrates. Scientific reports, 9(1), 1-11. PMID 31409866 PMC 6692315 doi:10.1038/s41598-019-48286-y

Further reading
  • Siswanto, F. M., Oguro, A., Arase, S., & Imaoka, S. (2020). WDR23 regulates the expression of Nrf2-driven drug-metabolizing enzymes. Drug Metabolism and Pharmacokinetics, 35(5), 441–455. PMID 32839090 doi:10.1016/j.dmpk.2020.06.007
  • Zhang, X., Luukkonen, L. M., Eissler, C. L., Crowley, V. M., Yamashita, Y., Schafroth, M. A., ... & Cravatt, B. F. (2021). DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras. Journal of the American Chemical Society, 143(13), 5141–5149. PMID 33783207 PMC 8309050 (available on 2022-04-07) doi:10.1021/jacs.1c00990
  • Le, R., Huang, Y., Zhang, Y., Wang, H., Lin, J., Dong, Y., ... & Gao, S. (2021). Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells. Cell Stem Cell, 28(4), 732–747. PMID 33357405 doi:10.1016/j.stem.2020.11.018
  • Wang, K., Liu, Y., Yu, Z., Gu, B., Hu, J., Huang, L., ... & Li, G. (2021). Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle. Cell reports, 37(6), 109987. PMID 34758320 doi:10.1016/j.celrep.2021.109987
  • Siswanto, F. M., Sakuma, R., Oguro, A., & Imaoka, S. (2022). Chlorogenic acid activates Nrf2/SKN-1 and prolongs the lifespan of Caenorhabditis elegans via the Akt-FOXO3/DAF16a-DDB1 pathway and activation of DAF16f. The Journals of Gerontology: Series A. glac062 PMID 35279029 doi:10.1093/gerona/glac062 Knockdown of WDR23, but not Keap1, abolished the effects of chlorogenic acid on the activation of Nrf2.


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