Quelle D E, Zindy F, Ashmun R A, Sherr C J
Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Cell. 1995 Dec 15;83(6):993-1000. doi: 10.1016/0092-8674(95)90214-7.
The INK4a (MTS1, CDKN2) gene encodes an inhibitor (p16INK4a) of the cyclin D-dependent kinases CDK4 and CDK6 that blocks them from phosphorylating the retinoblastoma protein (pRB) and prevents exit from the G1 phase of the cell cycle. Deletions and mutations involving INK4a occur frequently in cancers, implying that p16INK4a, like pRB, suppresses tumor formation. An unrelated protein (p19ARF) arises in major part from an alternative reading frame of the mouse INK4a gene, and its ectopic expression in the nucleus of rodent fibroblasts induces G1 and G2 phase arrest. Economical reutilization of coding sequences in this manner is practically without precedent in mammalian genomes, and the unitary inheritance of p16INK4a and p19ARF may underlie their dual requirement in cell cycle control.
INK4a（MTS1、CDKN2）基因编码一种细胞周期蛋白D依赖性激酶CDK4和CDK6的抑制剂（p16INK4a），该抑制剂可阻止它们磷酸化视网膜母细胞瘤蛋白（pRB），并防止细胞周期从G1期退出。涉及INK4a的缺失和突变在癌症中频繁发生，这意味着p16INK4a与pRB一样，可抑制肿瘤形成。一种不相关的蛋白质（p19ARF）主要来自小鼠INK4a基因的一个可变阅读框，其在啮齿动物成纤维细胞核中的异位表达会诱导G1期和G2期停滞。以这种方式对编码序列进行经济的再利用在哺乳动物基因组中几乎没有先例，p16INK4a和p19ARF的单一遗传可能是它们在细胞周期控制中双重需求的基础。
