Mindy1-KO Mouse

MINDY1, a member of the motif interacting with ubiquitin-containing novel DUB family, is a deubiquitinating enzyme. It has a key function in regulating protein stability by cleaving K48-linked polyubiquitin chains, thus affecting various biological processes and disease-related pathways [5].

In cancer research, MINDY1 has been found to play significant roles. In bladder cancer, MINDY1 depletion decreased cell proliferation by reducing YAP protein level and YAP/TEAD target genes expression, suggesting it promotes bladder cancer progression by stabilizing YAP [1]. In breast cancer, MINDY1 interacts with estrogen receptor α (ERα), mediates its deubiquitination, and increases its stability. MINDY1 depletion led to growth inhibition and cell cycle arrest of ERα-positive breast cancer cells [2]. In liver cancer, knocking out MINDY1 reduced the expression of stem markers, self-renewal ability of cells, and growth of transplanted tumors, and its high expression is an independent risk factor for poor prognosis [6]. Also, in breast and liver cancer, MINDY1 facilitates immune escape by maintaining the stability of immune checkpoint protein PD-L1 [7,8]. In muscle-related research, MINDY1 knockdown enhances insulin-stimulated glucose uptake in rat myotubes, linking it to insulin action in skeletal muscle [3]. In embryonic stem cells, high polyamine levels promote ESC self-renewal, in part, through maintaining high MINDY1 levels [4].

In conclusion, MINDY1 is a crucial deubiquitinating enzyme. Its function in stabilizing key proteins has a significant impact on cancer development, including bladder, breast, and liver cancer, as well as in processes like insulin action and embryonic stem cell self-renewal. Research using gene-knockout models in these areas has been instrumental in revealing these functions, providing potential therapeutic targets for related diseases.

References:

1. Luo, Yongwen, Zhou, Jun, Tang, Jianing, Liu, Tongzu, Liu, Tao. 2021. MINDY1 promotes bladder cancer progression by stabilizing YAP. In Cancer cell international, 21, 395. doi:10.1186/s12935-021-02095-4. https://pubmed.ncbi.nlm.nih.gov/34315490/

2. Tang, Jianing, Luo, Yongwen, Long, Guo, Zhou, Ledu. 2021. MINDY1 promotes breast cancer cell proliferation by stabilizing estrogen receptor α. In Cell death & disease, 12, 937. doi:10.1038/s41419-021-04244-z. https://pubmed.ncbi.nlm.nih.gov/34645792/

3. Needham, Elise J, Hingst, Janne R, Onslev, Johan D, James, David E, Wojtaszewski, Jørgen F P. 2024. Personalized phosphoproteomics of skeletal muscle insulin resistance and exercise links MINDY1 to insulin action. In Cell metabolism, 36, 2542-2559.e6. doi:10.1016/j.cmet.2024.10.020. https://pubmed.ncbi.nlm.nih.gov/39577414/

4. James, Christina, Zhao, Tian Yun, Rahim, Anisa, Dunn, Norris Ray, Vardy, Leah A. 2018. MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal. In Stem cells (Dayton, Ohio), 36, 1170-1178. doi:10.1002/stem.2830. https://pubmed.ncbi.nlm.nih.gov/29644784/

5. Abdul Rehman, Syed Arif, Armstrong, Lee A, Lange, Sven M, Svergun, Dmitri I, Kulathu, Yogesh. 2021. Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2. In Molecular cell, 81, 4176-4190.e6. doi:10.1016/j.molcel.2021.08.024. https://pubmed.ncbi.nlm.nih.gov/34529927/

6. Xia, B L, Liu, K W, Huang, H X, Wang, B, Gao, J. . [Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells]. In Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 31, 518-523. doi:10.3760/cma.j.cn501113-20230130-00028. https://pubmed.ncbi.nlm.nih.gov/37365029/

7. Ren, Liang, Wang, Li, Cao, Zhewei, Yang, Yang, Liu, Ya. 2024. Deubiquitinating Enzyme MINDY1 Facilitates Immune Escape in Breast Cancer by Maintaining the Stability of Immune Checkpoint Protein PD-L1. In The Tohoku journal of experimental medicine, , . doi:10.1620/tjem.2024.J111. https://pubmed.ncbi.nlm.nih.gov/39443136/

8. Song, Xingchao, Li, Wenjin, Tian, Chunyan, Yang, Weibin, Zhou, Jiahua. 2024. Study on the mechanism of liver cancer immune escape mediated by MINDY1 through regulation of PD-L1 ubiquitination level. In Biomolecules & biomedicine, 25, 144-154. doi:10.17305/bb.2024.10962. https://pubmed.ncbi.nlm.nih.gov/39217442/