Dnajc10, also known as ERdj5, is a member of the HSP40 family. It functions as a chaperone protein, often associated with endoplasmic reticulum stress response pathways, which are crucial for maintaining cellular homeostasis [1,2]. It has significant biological importance in processes like cell survival, self-renewal, and stress adaptation. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions.

In leukemia, Dnajc10 deficiency in an MLL-AF9-induced murine leukemia model led to a dramatic increase in apoptosis of leukemia cell lines and LSC-enriched populations, suppressing AML development and LSC self-renewal. Mechanistically, it regulates the PERK-EIF2α-ATF4 branch of the unfolded protein response (UPR) [1]. In mice with alcoholic liver disease, Dnajc10 knockout mice exhibited exacerbated alcohol-induced liver injury, hepatic steatosis, and oxidative stress, suggesting its protective role through the Nrf2 pathway and glutathione regulation [2].

In conclusion, Dnajc10 plays essential roles in maintaining cell survival, self-renewal, and protecting against oxidative stress. Findings from KO mouse models have revealed its significance in leukemia and alcoholic liver disease, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Li, Minjing, Wu, Xingli, Chen, Meiyang, Jin, Changzhu, Yin, Yancun. 2024. DNAJC10 maintains survival and self-renewal of leukemia stem cells through PERK branch of the unfolded protein response. In Haematologica, 109, 751-764. doi:10.3324/haematol.2023.282691. https://pubmed.ncbi.nlm.nih.gov/37496439/

2. Hong, Dong-Gyun, Song, Ga Yeon, Eom, Cheol Bin, Ko, Hyun-Jeong, Yang, Yoon Mee. 2022. Loss of ERdj5 exacerbates oxidative stress in mice with alcoholic liver disease via suppressing Nrf2. In Free radical biology & medicine, 184, 42-52. doi:10.1016/j.freeradbiomed.2022.03.027. https://pubmed.ncbi.nlm.nih.gov/35390453/