Dowdy S F, Hinds P W, Louie K, Reed S I, Arnold A, Weinberg R A
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Cell. 1993 May 7;73(3):499-511. doi: 10.1016/0092-8674(93)90137-f.
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 D1 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.
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可与pRb形成类似于几种病毒癌蛋白所形成的复合物，且这些复合物会被腺病毒E1A癌蛋白及其衍生肽破坏。这些细胞周期蛋白含有一个与病毒癌蛋白的pRb结合保守区域II基序相似的序列基序。细胞周期蛋白D1中该基序的改变会阻止细胞周期蛋白D1-pRb复合物的形成，同时增强在体内检测到的细胞周期蛋白D1的生物学活性。我们得出结论，细胞周期蛋白D1和D3与pRb的相互作用方式不同于可诱导pRb过度磷酸化的细胞周期蛋白A和E，并且细胞周期蛋白D1的活性可能受其与pRb结合的调节。
