Jun Jae Hee, Cha Hwayeon, Ko Je Yeong, Kim Ho-Shik, Yoo Kyung Hyun, Park Jong Hoon
Department of Biological Science, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
Sci Rep. 2025 Jan 16;15(1):2127. doi: 10.1038/s41598-025-86292-5.
Primary cilia are sensory organelles that regulate various signaling pathways. When microtubules are compared to a highway, motor proteins carry and transport cargo proteins, which are tuned by post-translational modifications, such as acetylation. However, the role of acetylation in primary cilia regulation remains unclear. In this study, histone K (lysine) acetyltransferase 2 B (Kat2b) was identified as a novel regulator of primary cilia. Kat2b, which mainly regulates transcription as a p300/CBP associated factor, is localized to the cytosol, centrosome, and cilium basal body. In addition, basal Kat2b expression gradually increased during ciliogenesis. Kat2b regulates the rate of cilia assembly, particularly in the early stages, and loss of Kat2b reduces the recruitment of intraflagellar transport (IFT) components to the ciliary axoneme and impairs Hedgehog (Hh) signaling activation. In addition, Kat2b-knockout mice showed mild abnormalities and ciliary IFT defects in the kidneys. These results establish a link between acetylation regulated by Kat2b and its relevance to ciliary assembly and function.
初级纤毛是调节各种信号通路的感觉细胞器。当将微管比作高速公路时，运动蛋白携带并运输货物蛋白，这些蛋白通过翻译后修饰（如乙酰化）进行调节。然而，乙酰化在初级纤毛调节中的作用仍不清楚。在本研究中，组蛋白K（赖氨酸）乙酰转移酶2B（Kat2b）被鉴定为初级纤毛的新型调节因子。Kat2b主要作为p300/CBP相关因子调节转录，定位于细胞质、中心体和纤毛基体。此外，在纤毛发生过程中，基础Kat2b表达逐渐增加。Kat2b调节纤毛组装速率，特别是在早期阶段，Kat2b的缺失会减少鞭毛内运输（IFT）成分向纤毛轴丝的募集，并损害刺猬（Hh）信号激活。此外，Kat2b基因敲除小鼠在肾脏中表现出轻度异常和纤毛IFT缺陷。这些结果建立了由Kat2b调节的乙酰化与其与纤毛组装和功能的相关性之间的联系。
