Dcaf13-KO Mouse

DCAF13, short for DDB1 and CUL4 associated factor 13, is a substrate receptor of the E3 ubiquitin ligase CRL4. It is involved in ubiquitination processes, which play crucial roles in regulating protein stability, function, and degradation, thus impacting various biological pathways and cellular functions [1,2,3,4]. Ubiquitination is essential for normal regulation of many biological functions such as cell cycle progression, DNA damage repair, and embryo development [4,5].

In disease-related research, DCAF13 has been found to be highly expressed in lung adenocarcinoma, ovarian cancer, and breast cancer, promoting cancer progression. In lung adenocarcinoma, it inhibits the p53 signaling pathway by promoting p53 ubiquitination and degradation, thus facilitating cancer cell proliferation and migration [1]. In ovarian cancer, it activates the FRAS1-mediated FAK signaling pathway by targeting FRAS1 for polyubiquitination and proteasomal degradation [2]. In breast cancer, it promotes cell proliferation by ubiquitin-inhibiting PERP expression [4]. Additionally, in preeclampsia, abnormal expression of DCAF13 affects endometrial decidualization, which may be involved in the occurrence and development of this pregnancy-related disorder [6]. In terms of embryo development, knockdown of DCAF13 in porcine embryos decreased blastocyst-stage development, affecting histone methylation-related gene expression and DNA damage repair [5]. In mice, uterine decidualization failed in pseudopregnant conditional Dcaf13 knockout mice, indicating its key role in decidualization [6]. Maternal-specific deletion of DCAF13 in mouse oocytes led to abnormal chromatin condensation and transcription in zygotic embryos, arresting development at the two-cell stage [7].

In summary, DCAF13 is essential for multiple biological processes, with its dysregulation contributing to various diseases. Gene knockout and conditional knockout mouse models have been pivotal in revealing its roles in cancer progression, embryo development, and preeclampsia, providing insights into potential therapeutic targets and disease mechanisms.

References:

1. Wei, Shan, Xing, Jing, Chen, Jia, Wang, Kai, Yu, Wanjun. 2024. DCAF13 inhibits the p53 signaling pathway by promoting p53 ubiquitination modification in lung adenocarcinoma. In Journal of experimental & clinical cancer research : CR, 43, 3. doi:10.1186/s13046-023-02936-2. https://pubmed.ncbi.nlm.nih.gov/38163876/

2. Tang, Ze-Yi, Wang, Xiao-Min, Xu, Chun-Wei, Cheng, Shu-Qun, Pan, Wei-Wei. 2024. DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway. In Cellular and molecular life sciences : CMLS, 81, 421. doi:10.1007/s00018-024-05446-2. https://pubmed.ncbi.nlm.nih.gov/39367995/

3. Ren, Peipei, Tong, Xiaomei, Li, Junjian, Zhang, Songying, Zhang, Yin-Li. 2024. CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes. In Cellular and molecular life sciences : CMLS, 81, 165. doi:10.1007/s00018-024-05185-4. https://pubmed.ncbi.nlm.nih.gov/38578457/

4. Shan, Bao-Qian, Wang, Xiao-Min, Zheng, Li, Pan, Wei-Wei, Zhang, Xin. 2022. DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression. In Cancer science, 113, 1587-1600. doi:10.1111/cas.15300. https://pubmed.ncbi.nlm.nih.gov/35178836/

5. da Silva, Zigomar, Glanzner, Werner Giehl, Gutierrez, Karina, Gonçalves, Paulo Bayard Dias, Bordignon, Vilceu. 2023. DCAF13 and RNF114 participate in the regulation of early porcine embryo development. In Reproduction (Cambridge, England), 166, 401-410. doi:10.1530/REP-23-0230. https://pubmed.ncbi.nlm.nih.gov/37855431/

6. Yan, Xingyu, Rong, Miaomiao, Zhou, Qianhui, Zhang, Cong. 2022. DCAF13 is essential for the pathogenesis of preeclampsia through its involvement in endometrial decidualization. In Molecular and cellular endocrinology, 556, 111741. doi:10.1016/j.mce.2022.111741. https://pubmed.ncbi.nlm.nih.gov/35932979/

7. Liu, Yang, Zhao, Long-Wen, Shen, Jing-Ling, Fan, Heng-Yu, Jin, Yan. 2019. Maternal DCAF13 Regulates Chromatin Tightness to Contribute to Embryonic Development. In Scientific reports, 9, 6278. doi:10.1038/s41598-019-42179-w. https://pubmed.ncbi.nlm.nih.gov/31000741/