Specific control of cell cycle entry by tyrosine phosphorylation of Cdk4

Cdk4 酪氨酸磷酸化对细胞周期进入的特异性控制

• 批准号: 08670139
• 负责人: JINNO Shigeki
• 金额: $ 1.41万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670139/
• 关键词: cell cycle; transformation; differentiation; cdk4; phosphorylation; cdk6; リン酸化

In higher eukaryote, a majority of cells are arrested in a quiescent state. The G0-G1 transition is important because G0 arrested cells must enter G1 phase of the cell cycle when they work. Recently we Rreported That Cdk4 is inactivated by phosphorylation on tyrosine 17 and that this inactivation is required for UV irradiation induced G1 checkpoint arrest. Here we show that this Cdk4 phosphorylation occurs only in a quiescent state and dephosphorylation during their cell cycle entry. In the cells traversing G1, Cdk4 is not tyrosine-phosphorylated. Ultraviolet irradiation blocks dephosphorylation, thereby preventing the "start" of the cell cycle. Exponentially growing cells are not able to arrestin G1 upon UV irradiation, because Cdk4 is not phosphory lated. We conclude that tyrosine phosphorylation of Cdk4 is specifically used for the control of the G0-G1 transition and constitutes a major DNA damage-responsive checkpoint mechanism during this transition.

在高等真核生物中，大多数细胞处于静止状态。G0-G1转变很重要，因为G0停滞的细胞在工作时必须进入细胞周期的G1期。最近，我们报道了CDK4是通过酪氨酸17的磷酸化失活的，这种失活是紫外线照射诱导的G1检查点停滞所必需的。在这里，我们表明，这种CDK4磷酸化只发生在静止状态，并在细胞周期进入时去磷酸化。在穿越G1的细胞中，CDK4不是酪氨酸磷酸化的。紫外线照射可阻止去磷酸化，从而阻止细胞周期的“开始”。指数生长的细胞不能在紫外线照射下产生arrestin G1，因为CDK4不是磷化的。我们得出结论，CDK4的酪氨酸磷酸化是专门用于控制G0-G1转变的，并在这一转变中构成了一个主要的DNA损伤反应检查点机制。

项目成果

Okayama, H.et al.: "Cell cycle control in fission yeast and mammals identification of new regulatory mechanisms." Adv.Cancer Research. 69. 17-62 (1996)

冈山，H.等人：“裂殖酵母的细胞周期控制和哺乳动物新调控机制的识别。”

Okayama,H.et.al.: "Cell cycle control in fission yeast and mammals:Identification of new regulatory mechanisms." Advances in Cencer Research. 69. 17-62 (1996)

冈山，H.等人：“裂殖酵母和哺乳动物的细胞周期控制：新调控机制的识别。”

Okayama,H.et.al.: "Cell cycle control in fission yeast and mammals:Identification of new regulatory mechanisms." Advances in Cancer Research. 69. 17-62 (1996)

冈山，H.等人：“裂殖酵母和哺乳动物的细胞周期控制：新调控机制的识别。”

Okayama, H., Nagata, A., Jinno, S., Murakami, H., Tanaka, K., and Nakashima, N.: "Cell cycle control in fission yeast and mammals identification of new regulatory mechanisms." Adv. Cancer Re.69. 17-62 (1996)

冈山 H.、永田 A.、神野 S.、村上 H.、田中 K. 和中岛 N.：“裂殖酵母中的细胞周期控制和哺乳动物新调控机制的识别。”