DCAF11

DCAF11
Identifiers
Aliases	DCAF11, PRO2389, WDR23, GL014, DDB1 and CUL4 associated factor 11
External IDs	OMIM: 613317 MGI: 90168 HomoloGene: 11886 GeneCards: DCAF11
Gene location (Human)
Chr.	Chromosome 14 (human)[1]
End	24,125,242 bp[1]
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)[2]
End	55,807,522 bp[2]
RNA expression pattern
	Top expressed in
	right lobe of liver; ; duodenum; ; body of pancreas; ; sural nerve; ; skeletal muscle tissue; ; blood; ; muscle of leg; ; bone marrow; ; gastrocnemius muscle; ; right adrenal gland;
	Top expressed in
	left lobe of liver; ; ankle; ; temporal muscle; ; right ventricle; ; sternocleidomastoid muscle; ; triceps brachii muscle; ; seminal vesicula; ; digastric muscle; ; vastus lateralis muscle; ; proximal tubule;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein binding;
Cellular component	Cul4-RING E3 ubiquitin ligase complex; nucleoplasm;
Biological process	post-translational protein modification; protein ubiquitination; proteasome-mediated ubiquitin-dependent protein catabolic process;
	Sources:Amigo / QuickGO
Orthologs
	80344
	28199
	ENSG00000100897; ENSG00000284796
	ENSMUSG00000022214
	Q8TEB1
	Q91VU6
	NM_001163484; NM_025230; NM_181357
	NM_001199009; NM_133734
	NP_001156956; NP_079506; NP_852002
	NP_001185938; NP_598495
	Wikidata
View/Edit Human	View/Edit Mouse

DDB1- and CUL4-associated factor 11 also known as WD Repeat Domain 23 (WDR23) is a protein that in humans is encoded by the DCAF11 gene.

DCAF11 is a WD40 repeat protein, containing seven repeats of the closed circular solenoid protein domain WD40.[5] The WDR23 locus is highly conserved from C. elegans to humans.[6] DCAF11/WDR23 is the E3 ligase that specifically targets proteins for degradation via ubiquitination.[7][8][9] 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.[10]

Dcaf11 is required for the alternative lengthening of telomeres in mouse embryos[11][12] especially at the 2C and four-cell stages of cleavage. The direct binding of DCAF11 in the region of distal enhancer of Zscan4 gene facilitates KAP1 removal by ubiquitination-mediated degradation, leading to a lower level of the repressive H3K9me3 marks and thus activates 2C-specific gene Zscan4.[12]

References

ENSG00000284796 GRCh38: Ensembl release 89: ENSG00000100897, ENSG00000284796 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000022214 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Choe KP, Przybysz AJ, Strange K (May 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. doi:10.1128/MCB.01811-08. PMC 2682033. PMID 19273594.
Tang L, Choe KP (July 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. doi:10.1016/j.mad.2015.06.001. PMID 26056713. S2CID 24399248.
Siswanto FM, Oguro A, Imaoka S (2021). "Sp1 is a substrate of Keap1 and regulates the activity of CRL4A^WDR23 ubiquitin ligase toward Nrf2". The Journal of Biological Chemistry. 296: 100704. doi:10.1016/j.jbc.2021.100704. PMC 8141886. PMID 33895141.
Chen Z, Wang K, Hou C, Jiang K, Chen B, Chen J, et al. (April 2017). "CRL4B^DCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells". Scientific Reports. 7 (1): 1175. doi:10.1038/s41598-017-01344-9. PMC 5430835. PMID 28446751.
Lo JY, Spatola BN, Curran SP (April 2017). "WDR23 regulates NRF2 independently of KEAP1". PLOS Genetics. 13 (4): e1006762. doi:10.1371/journal.pgen.1006762. PMC 5428976. PMID 28453520.
Spatola BN, Lo JY, Wang B, Curran SP (August 2019). "Nuclear and cytoplasmic WDR-23 isoforms mediate differential effects on GEN-1 and SKN-1 substrates". Scientific Reports. 9 (1): 11783. doi:10.1038/s41598-019-48286-y. PMC 6692315. PMID 31409866.
Dan J, Zhou Z, Wang F, Wang H, Guo R, Keefe DL, Liu L (January 2022). "Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells". Cells. 11 (3): 456. doi:10.3390/cells11030456. PMC 8834411. PMID 35159266.
Le R, Huang Y, Zhang Y, Wang H, Lin J, Dong Y, et al. (April 2021). "Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells". Cell Stem Cell. 28 (4): 732–747.e9. doi:10.1016/j.stem.2020.11.018. PMID 33357405. S2CID 229693249.

Siswanto FM, Oguro A, Arase S, Imaoka S (October 2020). "WDR23 regulates the expression of Nrf2-driven drug-metabolizing enzymes". Drug Metabolism and Pharmacokinetics. 35 (5): 441–455. doi:10.1016/j.dmpk.2020.06.007. PMID 32839090. S2CID 221307354.
Zhang X, Luukkonen LM, Eissler CL, Crowley VM, Yamashita Y, Schafroth MA, et al. (April 2021). "DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras". Journal of the American Chemical Society. 143 (13): 5141–5149. doi:10.1021/jacs.1c00990. PMC 8309050. PMID 33783207.
Le R, Huang Y, Zhang Y, Wang H, Lin J, Dong Y, et al. (April 2021). "Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells". Cell Stem Cell. 28 (4): 732–747.e9. doi:10.1016/j.stem.2020.11.018. PMID 33357405. S2CID 229693249.
Wang K, Liu Y, Yu Z, Gu B, Hu J, Huang L, et al. (November 2021). "Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle". Cell Reports. 37 (6): 109987. doi:10.1016/j.celrep.2021.109987. PMID 34758320. S2CID 243952009.
Siswanto FM, Sakuma R, Oguro A, Imaoka S (August 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, Biological Sciences and Medical Sciences. 77 (8): 1503–1516. doi:10.1093/gerona/glac062. PMID 35279029.

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[refGRCh38Ensembl-1] ENSG00000284796 GRCh38: Ensembl release 89: ENSG00000100897, ENSG00000284796 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022214 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Choe KP, Przybysz AJ, Strange K (May 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. doi:10.1128/MCB.01811-08. PMC 2682033. PMID 19273594.

[6] Tang L, Choe KP (July 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. doi:10.1016/j.mad.2015.06.001. PMID 26056713. S2CID 24399248.

[7] Siswanto FM, Oguro A, Imaoka S (2021). "Sp1 is a substrate of Keap1 and regulates the activity of CRL4A^WDR23 ubiquitin ligase toward Nrf2". The Journal of Biological Chemistry. 296: 100704. doi:10.1016/j.jbc.2021.100704. PMC 8141886. PMID 33895141.

[8] Chen Z, Wang K, Hou C, Jiang K, Chen B, Chen J, et al. (April 2017). "CRL4B^DCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells". Scientific Reports. 7 (1): 1175. doi:10.1038/s41598-017-01344-9. PMC 5430835. PMID 28446751.

[9] Lo JY, Spatola BN, Curran SP (April 2017). "WDR23 regulates NRF2 independently of KEAP1". PLOS Genetics. 13 (4): e1006762. doi:10.1371/journal.pgen.1006762. PMC 5428976. PMID 28453520.

[10] Spatola BN, Lo JY, Wang B, Curran SP (August 2019). "Nuclear and cytoplasmic WDR-23 isoforms mediate differential effects on GEN-1 and SKN-1 substrates". Scientific Reports. 9 (1): 11783. doi:10.1038/s41598-019-48286-y. PMC 6692315. PMID 31409866.

[11] Dan J, Zhou Z, Wang F, Wang H, Guo R, Keefe DL, Liu L (January 2022). "Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells". Cells. 11 (3): 456. doi:10.3390/cells11030456. PMC 8834411. PMID 35159266.

[Gao-12] Le R, Huang Y, Zhang Y, Wang H, Lin J, Dong Y, et al. (April 2021). "Dcaf11 activates Zscan4-mediated alternative telomere lengthening in early embryos and embryonic stem cells". Cell Stem Cell. 28 (4): 732–747.e9. doi:10.1016/j.stem.2020.11.018. PMID 33357405. S2CID 229693249.

DCAF11

References

Further reading