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首页> 外文期刊>Cell cycle >Multiple functions of D-type cyclins can antagonize pRb-mediated suppression of proliferation.
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Multiple functions of D-type cyclins can antagonize pRb-mediated suppression of proliferation.

机译：D型细胞周期蛋白的多种功能可以拮抗pRb介导的增殖抑制。

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The most well understood function of the D-type cyclins is to activate the G(1) kinases, cdk4 and cdk6, and target the retinoblastoma gene product (pRb) for phosphorylation and inactivation. pRb can suppress S phase entry, cause a transient G(1) arrest following DNA damage, and is critical in establishing terminal cell cycle withdrawal in cells exposed to differentiation or senescence-inducing signals. Each of these functions of pRb can be demonstrated in cultured cells derived from human tumors that have suffered RB1 gene inactivation. In such in vitro assays, coexpression of D type cyclins has been shown to inhibit the function of pRb, likely reflecting an oncogenic role of cyclin D1 in vivo. Two regions of cyclin D, the LxCxE pRb-binding motif, and the cyclin box, are thought to be critical for the proper function of cyclin D. Here we show that the LxCxE motif is dispensable in cyclin D1 for all functions tested, but is required by cyclin D2. This observation suggests that there is a functional difference between cyclins D1 and D2 in pRb regulation, and argues against complete functional redundancy of these D cyclins. In addition, the ability of cyclins D1 and D2 to activate cdk partners is required for induction of pRb phosphorylation and S phase entry. However, mutant forms of cyclins D1 and D2 that are incapable of activating kinase partners were still able to prevent pRb-induced senescence. Thus, D cyclins have both kinase-dependent and kinase-independent mechanisms of interfering with proliferation arrest and senescence.
机译：D型细胞周期蛋白最广为人知的功能是激活G（1）激酶cdk4和cdk6，并靶向视网膜母细胞瘤基因产物（pRb）进行磷酸化和失活。 pRb可以抑制S期进入，引起DNA损伤后短暂的G（1）停滞，并且在暴露于分化或衰老诱导信号的细胞中建立终末细胞周期撤回至关重要。 pRb的这些功能均可以在源自患有RB1基因失活的人类肿瘤的培养细胞中得到证实。在这种体外测定中，D型细胞周期蛋白的共表达已显示抑制pRb的功能，可能反映了细胞周期蛋白D1在体内的致癌作用。细胞周期蛋白D的两个区域，即LxCxE pRb结合基序和细胞周期蛋白框，被认为对细胞周期蛋白D的正常功能至关重要。在这里，我们证明LxCxE基序对于细胞周期蛋白D1对于所有测试的功能都是可有可无的。 cyclin D2所需。该观察结果表明细胞周期蛋白D1和D2在pRb调节方面存在功能差异，并反对这些D细胞周期蛋白的完全功能冗余。另外，细胞周期蛋白D1和D2激活cdk伴侣的能力是诱导pRb磷酸化和S期进入所必需的。但是，无法激活激酶伴侣的细胞周期蛋白D1和D2的突变形式仍然能够阻止pRb诱导的衰老。因此，D细胞周期蛋白具有干扰增殖抑制和衰老的激酶依赖性和激酶依赖性机制。

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