Hypoxia stimulates p16 expression and association with cdk4.
Hypoxia stimulates p16 expression and association with cdk4.
复制标题
缺氧刺激 p16 表达并与 cdk4 相关。
DOI：
10.1006/excr.2002.5564
复制
发表时间：
2002
影响因子：
3.7
通讯作者：
Krucher,NancyA
中科院分区：
文献类型：
--
作者：
Zygmunt,Adam;Tedesco,VivienneC;Udho,Eshwar;Krucher,NancyA
CV-1 P细胞暴露于缺氧条件下导致细胞增殖抑制，伴随着低磷酸化的生长抑制形式的pRb的积累。这部分是由于抑制了pRb导向的cdk 4和cdk 2活性。在这项研究中，我们试图阐明缺氧条件下cdk 4失活的机制。缺氧18 h后，CV-1 P细胞从G1期进入S期的进程受到抑制。这与丝氨酸-795的去磷酸化有关，丝氨酸-795是cdk 4的假定底物。缺氧18 h对CDK 4、CDK 6和D型细胞周期蛋白的表达无明显影响。分析了有氧或缺氧条件下cdki p16、p18、p19和p57的水平，尽管大多数cdki的水平不受缺氧条件的影响，但p16的水平在缺氧18小时时显著增加。缺氧条件下cdk 4活性被抑制的机制可能是通过p16与cdk 4的结合介导的。免疫沉淀分析表明，p16在缺氧条件下与cdk 4结合，但在有氧条件下不与cdk 4结合。因此，p16可能参与缺氧诱导的生长抑制。
Exposure of CV-1P cells to hypoxic conditions causes cell proliferation inhibition concomitant with the accumulation of pRb in the hypophosphorylated, growth suppressive form. This is in part due to inhibition of pRb-directed cdk4 and cdk2 activity. In this study we attempted to elucidate the mechanism by which cdk4 is inactivated under hypoxic conditions. After 18 h of hypoxia, CV-1P cells are inhibited from progressing from G1phase into the S phase of the cell cycle. This occurs in conjunction with dephosphorylation of serine-795, which is a putative substrate of cdk4. The amounts of cdk4, cdk6, and the D type cyclins are not affected by 18 h of hypoxia. The levels of cdki p16, p18, p19, and p57 under aerobic or hypoxic conditions were analyzed and although the levels of most cdki are unaffected by hypoxic conditions, the level of p16 increases significantly by 18 h of hypoxia. The mechanism by which cdk4 activity is inhibited under hypoxic conditions may be mediated through p16 association with cdk4. Immunoprecipitation analysis shows that p16 binds to cdk4 under hypoxic conditions but does not in cells maintained under aerobic conditions. Thus p16 may be involved in hypoxia-induced growth inhibition.