KAT2B, also known as PCAF (p300/CBP-associated factor), is a histone acetyltransferase. It plays a crucial role in regulating gene expression at the post-transcriptional level through acetylation. This process is involved in multiple biological pathways such as autophagy [2,6], and is also associated with various biological processes including cell development and metabolism [3]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable tools to study its functions.

In breast cancer, the NELF-E-SLUG-KAT2B epigenetic axis is crucial. Loss of the negative elongation factor (NELF) complex inhibits breast cancer development by down-regulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. KAT2B was identified as a key functional target of NELF-E-SLUG, and its genetic and pharmacological inactivation ameliorated the expression of EMT markers, phenocopying NELF ablation [1]. In cholangiocarcinoma, KAT2B is frequently down-regulated, and its overexpression suppressed cell proliferation and colony formation in vitro and inhibited tumor growth in mice. KAT2B enhanced the expression of the tumor suppressor gene NF2 via interaction with the transcription factor SP1, leading to inhibition of YAP activity [4]. In non-small cell lung cancer, KAT2B expression correlated positively with infiltrating levels of multiple immune cells and immune checkpoint genes. Low KAT2B expression was associated with poor prognosis and unsatisfactory efficacy of immune checkpoint blockade [5].

In conclusion, KAT2B is an important histone acetyltransferase involved in multiple biological processes. Through model-based research, especially KO/CKO mouse models, it has been revealed that KAT2B plays significant roles in cancer-related processes such as carcinogenesis, tumor growth regulation, and immune infiltration in diseases like breast cancer, cholangiocarcinoma, and non-small cell lung cancer.

References:

1. Zhang, Jieqiong, Hu, Zhenhua, Chung, Hwa Hwa, Tan, Ern Yu, Tee, Wee-Wei. 2023. Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis. In Nature communications, 14, 2439. doi:10.1038/s41467-023-38132-1. https://pubmed.ncbi.nlm.nih.gov/37117180/

2. Xu, Yinfeng, Wan, Wei. 2022. Acetylation in the regulation of autophagy. In Autophagy, 19, 379-387. doi:10.1080/15548627.2022.2062112. https://pubmed.ncbi.nlm.nih.gov/35435793/

3. Lin, Xiaoding, Li, Bo, Chen, Yuhan, Chen, Hong, Liu, Mei. 2022. KAT2B Gene Polymorphisms Are Associated with Body Measure Traits in Four Chinese Cattle Breeds. In Animals : an open access journal from MDPI, 12, . doi:10.3390/ani12151954. https://pubmed.ncbi.nlm.nih.gov/35953943/

4. Ma, Wenbo, Zhang, Jinqiang, Chen, Weina, Liu, Nianli, Wu, Tong. 2024. The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling. In Journal of experimental & clinical cancer research : CR, 43, 117. doi:10.1186/s13046-024-03036-5. https://pubmed.ncbi.nlm.nih.gov/38641672/

5. Zhou, Xue, Wang, Ning, Zhang, Yuefeng, Yu, Hongzhi, Wu, Qi. 2021. KAT2B is an immune infiltration-associated biomarker predicting prognosis and response to immunotherapy in non-small cell lung cancer. In Investigational new drugs, 40, 43-57. doi:10.1007/s10637-021-01159-6. https://pubmed.ncbi.nlm.nih.gov/34499335/

6. Huang, Hong, Ouyang, Qinqin, Mei, Kunrong, Liu, Wei, Liu, Rong. 2022. Acetylation of SCFD1 regulates SNARE complex formation and autophagosome-lysosome fusion. In Autophagy, 19, 189-203. doi:10.1080/15548627.2022.2064624. https://pubmed.ncbi.nlm.nih.gov/35465820/