p38α -: A suppressor of cell proliferation and tumorigenesis
p38α -: A suppressor of cell proliferation and tumorigenesis
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DOI：
10.4161/cc.6.20.4774
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发表时间：
2007-10-15
期刊：
影响因子：
4.3
通讯作者：
Wagner, Erwin F.
中科院分区：
文献类型：
--
作者：
Hui, Lijian;Bakiri, Latifa;Wagner, Erwin F.
丝裂原活化蛋白激酶（MAPK）p38 α参与许多生物学过程，并且是炎症相关疾病的药物靶标。对小鼠的遗传分析表明，由于胎盘发育受损，缺乏p38 α的胎儿是胚胎致死的。在使用p38 α的条件等位基因之前，p38 α在出生后小鼠中的功能仍不清楚。研究发现，p38 α对新生小鼠和成年小鼠的肺功能都是必不可少的。增殖增加和分化受损是p38 α缺陷细胞的标志。此外，使用致癌物或癌基因诱导的癌症模型，p38 α缺陷的小鼠易于发生癌症。p38 α可以通过拮抗JNK/c-Jun途径抑制细胞增殖，JNK/c-Jun途径是增殖和凋亡的重要调节因子。这些发现表明，p38的治疗性抑制可能导致不希望的增殖。因此，应考虑联合抑制p38和其他途径，如JNK途径，以靶向癌症炎症。
The mitogen-activated protein kinase (MAPK) p38 alpha is involved in numerous biological processes and is a drug target for inflammation-associated diseases. Genetic analysis in mice demonstrated that fetuses lacking p38 alpha are embryonic lethal owing to impaired placental development. The function of p38 alpha in mice after birth remained unclear until conditional alleles of p38 alpha were used. It was found that p38 alpha is essential for lung function in both neonatal and adult mice. Increased proliferation and impaired differentiation are the hallmarks of p38 alpha-deficient cells. Moreover, mice deficient in p38 alpha are prone to cancer development using carcinogen or oncogene-induced cancer models. p38 alpha can suppress cell proliferation by antagonizing the JNK/c-Jun pathway, which is an important regulator of proliferation and apoptosis. These findings suggest that therapeutic inhibition of p38 might lead to unwanted proliferation. Therefore, a combined inhibition of p38 and other pathways, such as the JNK pathway, should be considered for targeting cancer inflammation.