Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey Piscataway, New Jersey 08854, USA.
J Cell Biochem. 2011 Jul;112(7):1795-806. doi: 10.1002/jcb.23092.
The serine/threonine kinase PAK4 regulates cytoskeletal architecture, and controls cell proliferation and survival. In most adult tissues PAK4 is expressed at low levels, but overexpression of PAK4 is associated with uncontrolled proliferation, inappropriate cell survival, and oncogenic transformation. Here we have studied for the first time, the role for PAK4 in the cell cycle. We found that PAK4 levels peak dramatically but transiently in the early part of G1 phase. Deletion of Pak4 was also associated with an increase in p21 levels, and PAK4 was required for normal p21 degradation. In serum-starved cells, the absence of PAK4 led to a reduction in the amount of cells in G1, and an increase in the amount of cells in G2/M phase. We propose that the transient increase in PAK4 levels at early G1 reduces p21 levels, thereby abrogating the activity of CDK4/CDK6 kinases, and allowing cells to proceed with the cell cycle in a precisely coordinated way.
丝氨酸/苏氨酸激酶 PAK4 调节细胞骨架结构，并控制细胞增殖和存活。在大多数成年组织中，PAK4 的表达水平较低，但 PAK4 的过度表达与不受控制的增殖、不当的细胞存活和致癌转化有关。在这里，我们首次研究了 PAK4 在细胞周期中的作用。我们发现 PAK4 水平在 G1 期的早期急剧但短暂地达到峰值。Pak4 的缺失也与 p21 水平的增加有关，并且 PAK4 是正常 p21 降解所必需的。在血清饥饿的细胞中，缺乏 PAK4 导致 G1 期细胞数量减少，而 G2/M 期细胞数量增加。我们提出，在 G1 早期 PAK4 水平的短暂增加降低了 p21 水平，从而使 CDK4/CDK6 激酶失活，使细胞以精确协调的方式继续进行细胞周期。
