Ybx2, also known as Y-box binding protein 2, is a crucial modulator involved in multiple biological processes. It is essential for brown adipose tissue activation [1]. In addition, it has been associated with the properties of germ cells and cancer cells, influencing cancer stem-cell-like phenotypes in endometrial cancer [2,3]. It also plays a role in mRNA regulation processes, such as mRNA stability, translation, and degradation [2].

In brown adipocytes, phosphorylation of Ybx2 by AMPK at Thr115 or by Akt2 at Ser137 stabilizes Ybx2 by reducing ubiquitination-mediated degradation. This stabilized Ybx2 promotes glycolysis by assisting the expression of glycolytic enzymes, modulating the translation of glycolytic genes via direct binding to their 5'-UTRs [1]. In endometrial cancer cells, Ybx2 regulates RNA stability through interaction with the m6A reader protein YTHDF2 [2]. In round spermatids of Ybx2-knockout mouse models, mRNAs like Prm1 and Smcp are prematurely recruited onto polysomes, indicating Ybx2's role in repressing mRNA translation and blocking translation-dependent mRNA decay in round spermatids [4].

In conclusion, Ybx2 has diverse essential functions. It is responsive to thermogenic stimuli in brown adipocytes, regulating glycolysis and thermogenesis. In cancer, especially endometrial cancer, it contributes to stem-like phenotypes and chemoresistance. The study of Ybx2 using gene-knockout mouse models has provided insights into its role in these biological processes and disease conditions, potentially guiding future research on related diseases.

References:

1. Zhao, Qingwen, Yu, Chao, Xu, Xiaoxuan, Gao, Yue, Pan, Dongning. 2023. Phosphorylated YBX2 is stabilized to promote glycolysis in brown adipocytes. In iScience, 26, 108091. doi:10.1016/j.isci.2023.108091. https://pubmed.ncbi.nlm.nih.gov/37860762/

2. Cai, Ying, Li, Na, Li, Huaibiao. 2023. YBX2 modulates mRNA stability via interaction with YTHDF2 in endometrial cancer cells. In Experimental cell research, 427, 113586. doi:10.1016/j.yexcr.2023.113586. https://pubmed.ncbi.nlm.nih.gov/37030331/

3. Suzuki, Izumi, Yoshida, Sachiko, Tabu, Kouichi, Takeda, Satoru, Kato, Kiyoko. 2021. YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer. In Scientific reports, 11, 4220. doi:10.1038/s41598-021-83200-5. https://pubmed.ncbi.nlm.nih.gov/33602962/

4. Kleene, Kenneth C. 2016. Position-dependent interactions of Y-box protein 2 (YBX2) with mRNA enable mRNA storage in round spermatids by repressing mRNA translation and blocking translation-dependent mRNA decay. In Molecular reproduction and development, 83, 190-207. doi:10.1002/mrd.22616. https://pubmed.ncbi.nlm.nih.gov/26773323/