Transduced p16INK4a peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1.
Transduced p16INK4a peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1.
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发表时间：
1999-06
期刊：
影响因子：
11.2
通讯作者：
David Gius;S. Ezhevsky;M. Becker-Hapak;Hikaru Nagahara;Michael C. Wei;Steven F. Dowdy
中科院分区：
文献类型：
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作者：
David Gius;S. Ezhevsky;M. Becker-Hapak;Hikaru Nagahara;Michael C. Wei;Steven F. Dowdy
细胞通过细胞周期的G1期的进展需要细胞周期蛋白D：Cdk 4/6和细胞周期蛋白E：Cdk 2复合物;然而，这些复合物的持续时间和顺序仍然不清楚。为了解决这个问题，我们合成了一个肽基模拟的Cdk 4/6抑制剂，p16 INK 4a，含有一个NH 2-末端达特蛋白转导结构域。转导TAT-p16野生型肽进入细胞导致活性，低磷酸化pRb的损失，并引起早期G1细胞周期停滞，提供细胞周期蛋白E：Cdk 2复合物是无活性的。我们的结论是，细胞周期蛋白D：Cdk 4/6活性所需的早期G1期细胞周期的进展，但不超过，激活细胞周期蛋白E：Cdk 2复合物的限制点，因此是非冗余的细胞周期蛋白E：Cdk 2在G1晚期。
Progression of cells through the G1 phase of the cell cycle requires cyclin D:Cdk4/6 and cyclin E:Cdk2 complexes; however, the duration and ordering of these complexes remain unclear. To address this, we synthesized a peptidyl mimetic of the Cdk4/6 inhibitor, p16INK4a that contained an NH2-terminal TAT protein transduction domain. Transduction of TAT-p16 wild-type peptides into cells resulted in the loss of active, hypophosphorylated pRb and elicited an early G1 cell cycle arrest, provided cyclin E:Cdk2 complexes were inactive. We conclude that cyclin D:Cdk4/6 activity is required for early G1 phase cell cycle progression up to, but not beyond, activation of cyclin E:Cdk2 complexes at the restriction point and is thus nonredundant with cyclin E:Cdk2 in late G1.