Sakamaki Toshiyuki, Casimiro Mathew C, Ju Xiaoming, Quong Andrew A, Katiyar Sanjay, Liu Manran, Jiao Xuanmao, Li Anping, Zhang Xueping, Lu Yinan, Wang Chenguang, Byers Stephen, Nicholson Robert, Link Todd, Shemluck Melvin, Yang Jianguo, Fricke Stanley T, Novikoff Phyllis M, Papanikolaou Alexandros, Arnold Andrew, Albanese Christopher, Pestell Richard
Departments of Cancer Biology, Thomas Jefferson University, BLSB, Room 1050, 233 South 10th Street, Philadelphia, PA 19107, USA.
Mol Cell Biol. 2006 Jul;26(14):5449-69. doi: 10.1128/MCB.02074-05.
The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient for the development of murine mammary tumors. Herein, cyclin D1 is shown to perform a novel function, inhibiting mitochondrial function and size. Mitochondrial activity was enhanced by genetic deletion or antisense or small interfering RNA to cyclin D1. Global gene expression profiling and functional analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and mitochondrial function.
细胞周期蛋白D1基因编码全酶的一个调节亚基，该亚基使视网膜母细胞瘤肿瘤抑制因子磷酸化并使其失活，从而促进核DNA合成。细胞周期蛋白D1在人类乳腺癌中过表达，并且足以引发小鼠乳腺肿瘤。在此，细胞周期蛋白D1被证明具有一种新功能，即抑制线粒体功能和大小。通过对细胞周期蛋白D1进行基因缺失、反义或小干扰RNA处理，可增强线粒体活性。对乳腺上皮细胞靶向的细胞周期蛋白D1反义转基因小鼠进行全基因组表达谱分析和功能分析表明，细胞周期蛋白D1在体内抑制线粒体活性和有氧糖酵解。在细胞周期蛋白D1诱导的乳腺肿瘤中观察到这些基因的相互调节。因此，细胞周期蛋白D1整合了核DNA合成和线粒体功能。
