COLLABORATION OF G(1) CYCLINS IN THE FUNCTIONAL INACTIVATION OF THE RETINOBLASTOMA PROTEIN
COLLABORATION OF G(1) CYCLINS IN THE FUNCTIONAL INACTIVATION OF THE RETINOBLASTOMA PROTEIN
复制标题
DOI：
10.1101/gad.8.15.1759
复制
发表时间：
1994-08-01
影响因子：
10.5
通讯作者：
WEINBERG, RA
中科院分区：
文献类型：
--
作者：
HATAKEYAMA, M;BRILL, JA;WEINBERG, RA
视网膜母细胞瘤基因产物(Prb)通过阻止细胞周期从G(1)期进入S期而抑制细胞增殖。它的生长抑制作用似乎被G(1)期间发生的过度磷酸化逆转。这一过程被认为涉及G(1)细胞周期蛋白和细胞周期蛋白依赖性蛋白激酶(CDK)。在此，我们报道了哺乳动物pRb依赖于细胞周期的磷酸化在酿酒酵母中表达后得到了忠实的复制。就像哺乳动物的情况一样，这种磷酸化需要一个完整的癌蛋白结合域，并被负生长因子抑制，在这种情况下是交配信息素。PRb在cln(-)突变体中的表达表明，酵母中pRb的过度磷酸化需要内源G(1)细胞周期蛋白、Cln3和Cln1或Cln2的特定组合。此外，哺乳动物细胞周期蛋白G(1)在CLN(-)酵母细胞中的表达表明，Cln2和Cln3在pRb过度磷酸化中的作用可分别被人细胞周期蛋白E和细胞周期蛋白D1所互补。这些观察表明G(1)Cyclin-cdk复合体之间存在功能异质性，并表明需要多个G(1)Cyclins参与促进pRb过度磷酸化和由此导致的细胞周期进展。
The retinoblastoma gene product (pRB) constrains cell proliferation by preventing cell-cycle progression from the G(1) to S phase. Its growth-inhibitory effects appear to be reversed by hyperphosphorylation occurring during G(1). This process is thought to involve G(1) cyclins and cyclin-dependent kinases (cdks). Here we report that the cell cycle-dependent phosphorylation of mammalian pRB is faithfully reproduced when it is expressed in Saccharomyces cerevisiae. As is the case in mammalian tells, this phosphorylation requires an intact oncoprotein-binding domain and is inhibited by a negative growth factor, in this case a mating pheromone. Expression of pRB in cln (-) mutants indicates that specific combinations of endogenous G(1) cyclins, Cln3 and either Cln1 or Cln2 are required for pRB hyperphosphorylation in yeast. Moreover, expression of mammalian G(1) cyclins in cln (-) yeast cells indicates that the functions of Cln2 and Cln3 in pRB hyperphosphorylation can be complemented by human cyclin E and cyclin D1, respectively. These observations suggest a functional heterogeneity among G(1) cyclin-cdk complexes and indicate a need for the involvement of multiple G(1) cyclins in promoting pRB hyperphosphorylation and resulting cell-cycle progression.