TTLL12, a member of the Tubulin Tyrosine Ligase-Like (TTLL) family, has functions in histone methylation and affects tubulin tyrosine ligase activities [1,5]. It is involved in multiple biological pathways, including those related to ciliogenesis, antiviral response, and cancer-related processes. Its study is crucial for understanding various cellular mechanisms and disease development. Genetic models, such as KO or CKO mouse models, could potentially provide more insights into its in-vivo functions.

In ovarian cancer, TTLL12 expression is significantly increased compared to normal ovarian tissues and cell lines, and is associated with FIGO stage, peritoneal cytology, and is an independent risk factor for overall and disease-free survival, suggesting it as a potential molecular marker for predicting invasion and progression [1]. In polarized renal epithelial cells, TTLL12 localizes to the base of primary cilia and is required for cilia formation, directly binds to the α/β-tubulin heterodimer, and regulates microtubule dynamics, stability, and post-translational modifications [2,4]. It uniquely promotes microtubule lysine acetylation and arginine methylation [2,4]. In the antiviral signaling pathway, TTLL12 is a negative regulator of RIG-I signaling, repressing IFN-β expression induced by Sendai virus, and its deficiency increases IFN-β expression and inhibits virus replication [3]. In prostate cancer, TTLL12 expression increases during cancer progression to metastasis, and its down-regulation affects tubulin post-translational modifications and overexpression alters chromosomal ploidy, suggesting it could contribute to tumorigenesis [6]. In gastric adenocarcinoma, high levels of TTLL12 are associated with early and advanced stages, lymph nodes, distant metastases, and risk factors like H. pylori [7].

In summary, TTLL12 is involved in multiple biological processes. Its role in primary ciliary axoneme formation, antiviral response, and cancer-related processes has been revealed through functional studies. Although no KO/CKO mouse model-specific findings were in the references, understanding TTLL12's functions can potentially provide insights into disease mechanisms in areas such as cancer, ciliopathies, and antiviral immunity.

References:

1. Yang, Shangjie, Liang, Yanping, Qian, Haihong, Li, Qiuhong. 2020. TTLL12 expression in ovarian cancer correlates with a poor outcome. In International journal of clinical and experimental pathology, 13, 239-247. doi:. https://pubmed.ncbi.nlm.nih.gov/32211104/

2. Ceglowski, J, Hoffman, H K, Hoff, K J, Moore, J K, Prekeris, R. 2023. TTLL12 is required for primary ciliary axoneme formation in polarized epithelial cells. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.07.25.550533. https://pubmed.ncbi.nlm.nih.gov/37546873/

3. Ju, Lin-Gao, Zhu, Yuan, Lei, Pin-Ji, Li, Lian-Yun, Wu, Min. 2016. TTLL12 Inhibits the Activation of Cellular Antiviral Signaling through Interaction with VISA/MAVS. In Journal of immunology (Baltimore, Md. : 1950), 198, 1274-1284. doi:10.4049/jimmunol.1601194. https://pubmed.ncbi.nlm.nih.gov/28011935/

4. Ceglowski, Julia, Hoffman, Huxley K, Neumann, Andrew J, Moore, Jeffrey K, Prekeris, Rytis. 2023. TTLL12 is required for primary ciliary axoneme formation in polarized epithelial cells. In EMBO reports, 25, 198-227. doi:10.1038/s44319-023-00005-5. https://pubmed.ncbi.nlm.nih.gov/38177908/

5. Wen, Ruiling, Xiao, Yingying, Zhang, Yuhua, Lin, Yongping, Tang, Jun. 2016. Identification of a novel transcript isoform of the TTLL12 gene in human cancers. In Oncology reports, 36, 3172-3180. doi:10.3892/or.2016.5135. https://pubmed.ncbi.nlm.nih.gov/27748896/

6. Wasylyk, Christine, Zambrano, Alberto, Zhao, Chunhua, Klocker, Helmut, Wasylyk, Bohdan. . Tubulin tyrosine ligase like 12 links to prostate cancer through tubulin posttranslational modification and chromosome ploidy. In International journal of cancer, 127, 2542-53. doi:10.1002/ijc.25261. https://pubmed.ncbi.nlm.nih.gov/20162578/

7. Heitor da Silva Maués, Jersey, Ferreira Ribeiro, Helem, de Maria Maués Sacramento, Raquel, de Fátima Aquino Moreira-Nunes, Caroline, Mário Rodriguez Burbano, Rommel. 2020. Downregulated genes by silencing MYC pathway identified with RNA-SEQ analysis as potential prognostic biomarkers in gastric adenocarcinoma. In Aging, 12, 24651-24670. doi:10.18632/aging.202260. https://pubmed.ncbi.nlm.nih.gov/33351778/