Dnajb8-KO Mouse

Dnajb8, a member of the heat shock protein 40 (HSP40) family, is a J-domain protein (JDP) molecular chaperone. JDPs are central in maintaining a healthy proteome. Dnajb8 is involved in various cellular processes such as protein folding, and it may interact with pathways related to stress response, autophagy, and drug resistance [1,2,3,4]. Genetic models, like knockout mice, can be valuable in studying its functions.

In a knockout (KO) mouse model, Dnajb8 was found dispensable for spermatogenesis and male fertility [5]. In renal cell carcinoma cell lines, Dnajb8 KO cells showed reduced side population cells, decreased sphere-forming ability, and increased sensitivity to Docetaxel, indicating its role in tumor initiation and drug resistance [6]. Treatment with siRNA targeting Dnajb8 restored Oxaliplatin sensitivity in colon cancer cells in vitro and in vivo, as Dnajb8 promotes Oxaliplatin resistance through the TP53/MDR1 pathway [2]. DNAJB8 also restricts HIV-1 virion infectivity by facilitating autophagic-lysosomal degradation of viral Vif protein and rescuing APOBEC3G expression [3]. It inhibits pseudorabies virus replication by promoting cellular autophagy [4].

In conclusion, Dnajb8 plays diverse roles in biological processes. Model-based research, especially KO mouse models, has revealed its significance in cancer drug resistance, viral infections, and male fertility-related processes. Understanding Dnajb8's functions provides insights into disease mechanisms and potential therapeutic targets for conditions like colon cancer, HIV-1 infection, and pseudorabies virus-related diseases.

References:

1. Ryder, Bryan D, Ustyantseva, Elizaveta, Boyer, David R, Kampinga, Harm H, Joachimiak, Lukasz A. 2024. DNAJB8 oligomerization is mediated by an aromatic-rich motif that is dispensable for substrate activity. In Structure (London, England : 1993), 32, 662-678.e8. doi:10.1016/j.str.2024.02.015. https://pubmed.ncbi.nlm.nih.gov/38508190/

2. Wang, Zheng, Li, Yi, Mao, Rui, Liu, Yanjun, Zhang, Tongtong. 2022. DNAJB8 in small extracellular vesicles promotes Oxaliplatin resistance through TP53/MDR1 pathway in colon cancer. In Cell death & disease, 13, 151. doi:10.1038/s41419-022-04599-x. https://pubmed.ncbi.nlm.nih.gov/35165262/

3. Chand, Kailash, Barman, Muneesh Kumar, Ghosh, Payel, Mitra, Debashis. . DNAJB8 facilitates autophagic-lysosomal degradation of viral Vif protein and restricts HIV-1 virion infectivity by rescuing APOBEC3G expression in host cells. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e22793. doi:10.1096/fj.202201738R. https://pubmed.ncbi.nlm.nih.gov/36723955/

4. Chen, Xiaoyong, Li, Wenfeng. 2024. The heat shock protein DNAJB8 inhibits pseudorabies virus replication by autophagy. In Veterinary microbiology, 295, 110165. doi:10.1016/j.vetmic.2024.110165. https://pubmed.ncbi.nlm.nih.gov/38936156/

5. Wang, Fengsong, Kong, Shuai, Hu, Xuechun, Ye, Lan, Bai, Shun. 2020. Dnajb8, a target gene of SOX30, is dispensable for male fertility in mice. In PeerJ, 8, e10582. doi:10.7717/peerj.10582. https://pubmed.ncbi.nlm.nih.gov/33391882/

6. Yamashita, Masamichi, Hirohashi, Yoshihiko, Torigoe, Toshihiko, Imagawa, Tomohiro, Sato, Noriyuki. 2016. Dnajb8, a Member of the Heat Shock Protein 40 Family Has a Role in the Tumor Initiation and Resistance to Docetaxel but Is Dispensable for Stress Response. In PloS one, 11, e0146501. doi:10.1371/journal.pone.0146501. https://pubmed.ncbi.nlm.nih.gov/26751205/