DCAF11

DCAF11 (DDB1- and CUL4-associated factor 11, also known as WDR23) is a WD40 repeat-containing substrate receptor of the CRL4 (CUL4-DDB1) E3 ubiquitin ligase complex, where it contributes to ubiquitin-dependent regulation of protein stability and cellular signaling pathways.^[1][2] Mechanistically, DCAF11 functions within the cullin-RING ubiquitination machinery and has been shown to mediate substrate ubiquitination and proteasomal degradation, linking it to the control of genome integrity and protein homeostasis.^[2][3] In developmental and stem-cell contexts, DCAF11 promotes ZSCAN4-mediated alternative telomere lengthening (ALT) by targeting KAP1 for ubiquitination-dependent degradation, thereby activating ZSCAN4-associated transcriptional programs and facilitating telomere elongation in early embryos and embryonic stem cells.^[4] Loss of DCAF11 reduces telomere sister-chromatid exchange and impairs telomere maintenance, supporting a functional role in chromosome stability and stem-cell fitness.^[4] DCAF11 also participates in cell-cycle regulation through ubiquitination-dependent degradation of CENP-A, indicating broader functions in chromatin and centromere homeostasis.^[5] Compared with related DCAF family substrate receptors, DCAF11 has attracted particular interest because it can be directly engaged by electrophilic small molecules and serves as a recruitable E3 ligase for targeted protein degradation (TPD) technologies.^[3][6][7] Recent studies identified covalent ligand classes, including arylidene-indolinones and cyanoacrylamide-containing degraders, that exploit DCAF11 to induce selective proteasomal degradation of target proteins, expanding the experimental toolbox for chemical biology and degrader discovery.^[3][6][7]

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