Tbl1xr1, also known as transducin (beta)-like 1X related protein 1, is an integral subunit of the NCoR and SMRT repressor complexes. It is evolutionarily conserved and essential for transcriptional repression by unliganded nuclear receptors and other transcription factors. Additionally, it can act as a transcription activator. Tbl1xr1 is required for the activation of multiple intracellular signaling pathways and is widely distributed in various tissues such as the pituitary, hypothalamus, adipose tissue, muscle, and liver [1].

In mice, Tbl1xr1 deficiency reduces spermatozoa motility and disrupts histone-to-protamine transition, indicating its role in male fertility [2]. Tbl1xr1 knock-out mice also exhibit behavioral and neuronal abnormalities, with decreased neural progenitor proliferation and increased differentiation due to a failure in MAPK cascade regulation [3]. In B-lymphoblastic leukemia, loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin, resulting in glucocorticoid resistance [1].

In conclusion, Tbl1xr1 is crucial for transcriptional regulation and the activation of intracellular signaling pathways. Studies using gene knockout mouse models have revealed its roles in male fertility, neural development, and response to glucocorticoids in leukemia. These findings enhance our understanding of the biological functions of Tbl1xr1 and its implications in various disease conditions.

References:

1. Li, Jian Yi, Daniels, Garrett, Wang, Jing, Zhang, Xinmin. 2015. TBL1XR1 in physiological and pathological states. In American journal of clinical and experimental urology, 3, 13-23. doi:. https://pubmed.ncbi.nlm.nih.gov/26069883/

2. Zhou, Qiao, Xu, Miaofei, Wang, Xin, Ling, Xiufeng, Ji, Juan. 2021. Deficiency of TBL1XR1 causes asthenozoospermia. In Andrologia, 53, e13980. doi:10.1111/and.13980. https://pubmed.ncbi.nlm.nih.gov/33528066/

3. Mastrototaro, Giuseppina, Zaghi, Mattia, Massimino, Luca, Herzig, Stephan, Sessa, Alessandro. 2021. TBL1XR1 Ensures Balanced Neural Development Through NCOR Complex-Mediated Regulation of the MAPK Pathway. In Frontiers in cell and developmental biology, 9, 641410. doi:10.3389/fcell.2021.641410. https://pubmed.ncbi.nlm.nih.gov/33708771/