PHYSICAL INTERACTION OF THE RETINOBLASTOMA PROTEIN WITH HUMAN D-CYCLINS
PHYSICAL INTERACTION OF THE RETINOBLASTOMA PROTEIN WITH HUMAN D-CYCLINS
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DOI：
10.1016/0092-8674(93)90137-f
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发表时间：
1993-05-07
期刊：
影响因子：
64.5
通讯作者：
WEINBERG, RA
中科院分区：
文献类型：
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作者：
DOWDY, SF;HINDS, PW;WEINBERG, RA
视网膜母细胞瘤蛋白（pRb）作为细胞增殖的调节因子，反过来又受细胞周期蛋白依赖性激酶的调节。细胞周期蛋白D1和D3可以与pRb形成类似于几种病毒癌蛋白形成的复合物，并被腺病毒E1A癌蛋白和衍生肽破坏。这些细胞周期蛋白含有一个序列基序，类似于病毒癌蛋白的prb结合保守区II基序。cyclin Dl中该基序的改变阻止了cyclin D1- prb复合物的形成，同时增强了cyclin D1在体内的生物活性。我们得出结论，细胞周期蛋白D1和D3以不同于细胞周期蛋白a和E的方式与pRb相互作用，可以诱导pRb过度磷酸化，并且细胞周期蛋白D1的活性可能通过其与pRb的关联而受到调节。
The retinoblastoma protein (pRb) functions as a regulator of cell proliferation and in turn is regulated by cyclin-dependent kinases. Cyclins D1 and D3 can form complexes with pRb that resemble those formed by several viral oncoproteins and are disrupted by the adenovirus E1A oncoprotein and derived peptides. These cyclins contain a sequence motif similar to the pRb-binding conserved region II motif of the viral oncoproteins. Alteration of this motif in cyclin Dl prevents formation of cyclin D1-pRb complexes while enhancing the biological activity of cyclin D1 assayed in vivo. We conclude that cyclins D1 and D3 interact with pRb in a fashion distinct from cyclins A and E, which can induce pRb hyperphosphorylation, and that cyclin D1 activity may be regulated by its association with pRb.