Awad M M, Sanders J A, Gruppuso P A
Department of Pediatrics, Rhode Island Hospital and Brown University School of Medicine, 593 Eddy Street, Providence, RI 02903, USA.
FEBS Lett. 2000 Oct 20;483(2-3):160-4. doi: 10.1016/s0014-5793(00)02108-6.
Hepatocytes undergo marked changes in proliferation during normal liver development. In order to elucidate the mechanism for these changes, we examined the ontogeny of expression for the known cyclin-dependent kinase inhibitors (CKIs), p15(Ink4b), p16(Ink4a), p18(Ink4c), p19(Ink4d), p21(Cip1), p27(Kip1) and p57(Kip2). All except p16(Ink4a) were expressed at some time between late gestation and adulthood. The mRNA and protein expression patterns for p15(Ink4b) and p57(Kip2) were consistent with a role for these CKIs in the regulation of hepatocyte proliferation. Specifically, p57(Kip2) may contribute to hepatocyte growth arrest that occurs in term fetuses, while p15(Ink4b) may contribute to the maintenance of adult hepatocytes in a quiescent state. These results assign a possible role to two CKIs not previously identified as involved in hepatocyte cell cycle control.
在正常肝脏发育过程中,肝细胞的增殖会发生显著变化。为了阐明这些变化的机制,我们研究了已知的细胞周期蛋白依赖性激酶抑制剂(CKIs)p15(Ink4b)、p16(Ink4a)、p18(Ink4c)、p19(Ink4d)、p21(Cip1)、p27(Kip1)和p57(Kip2)的表达个体发生情况。除p16(Ink4a)外,所有这些抑制剂在妊娠晚期至成年期的某个时间均有表达。p15(Ink4b)和p57(Kip2)的mRNA和蛋白质表达模式与这些CKIs在肝细胞增殖调节中的作用一致。具体而言,p57(Kip2)可能有助于足月胎儿中发生的肝细胞生长停滞,而p15(Ink4b)可能有助于维持成年肝细胞处于静止状态。这些结果为两种先前未被确定参与肝细胞细胞周期控制的CKIs赋予了可能的作用。