Division of Reconstructive Surgery for Oral and Maxillofacial Region, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan; Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Biochem Biophys Res Commun. 2021 Jun 11;557:294-301. doi: 10.1016/j.bbrc.2021.04.021. Epub 2021 Apr 21.
Pontin and Reptin are closely related proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They form a hetero-oligomeric complex, Pontin/Reptin, which is involved in protein stability and assembly of the protein complexes as a molecular chaperone. Overexpression of Pontin and Reptin in tumor cells has been reported and is implicated in the development of various cancers. However, the molecular mechanism of Pontin/Reptin function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we identify HEAT repeat-containing protein 1 (HEATR1) as a novel binding factor of Pontin/Reptin. Functionally, HEATR1 stabilizes Pontin/Reptin and positively regulates OSCC cell proliferation by activating mTOR and pre-rRNA synthesis. We also find that HEATR1 expression is markedly upregulated in tumor region of OSCC tissue. Hence, we propose that HEATR1 is involved in the regulation of mTOR and ribosome biogenesis as a potential protein stabilizer of Pontin/Reptin in OSCC.
Pontin 和 Reptin 是密切相关的蛋白，属于 AAA+（与各种细胞活动相关的 ATP 酶）家族。它们形成异源寡聚体复合物，Pontin/Reptin，作为分子伴侣参与蛋白质稳定性和蛋白质复合物的组装。在肿瘤细胞中已经报道了 Pontin 和 Reptin 的过表达，并与各种癌症的发生有关。然而，Pontin/Reptin 在口腔鳞状细胞癌（OSCC）发展中的功能的分子机制尚不清楚。在这里，我们鉴定出热休克蛋白 HEATR1 是 Pontin/Reptin 的一个新的结合因子。在功能上，HEATR1 稳定 Pontin/Reptin，并通过激活 mTOR 和 pre-rRNA 合成正向调节 OSCC 细胞增殖。我们还发现 HEATR1 在 OSCC 组织的肿瘤区域表达明显上调。因此，我们提出 HEATR1 作为 Pontin/Reptin 的潜在蛋白稳定剂，参与 mTOR 和核糖体生物发生的调节。
