p38alpha: a suppressor of cell proliferation and tumorigenesis.
p38alpha: a suppressor of cell proliferation and tumorigenesis.
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发表时间：
2007
期刊：
影响因子：
4.3
通讯作者：
Lijian Hui;L. Bakiri;Ewa Stepniak;E. Wagner
中科院分区：
文献类型：
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作者：
Lijian Hui;L. Bakiri;Ewa Stepniak;E. Wagner
丝裂原活化蛋白激酶（MAPK） p38α参与许多生物过程，是炎症相关疾病的药物靶点。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条件等位基因之前，p38 α在小鼠出生后的功能尚不清楚。研究发现，p38 α对新生小鼠和成年小鼠的肺功能都至关重要。增殖增加和分化受损是p38α缺陷细胞的特征。此外，在致癌物或癌基因诱导的癌症模型中，缺乏p38 α的小鼠更容易发生癌症发展。p38alpha通过拮抗JNK/c-Jun通路抑制细胞增殖，是细胞增殖和凋亡的重要调控因子。这些发现表明p38的治疗性抑制可能导致不必要的增殖。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) p38alpha is involved in numerous biological processes and is a drug target for inflammation-associated diseases. Genetic analysis in mice demonstrated that fetuses lacking p38alpha are embryonic lethal owing to impaired placental development. The function of p38alpha in mice after birth remained unclear until conditional alleles of p38alpha were used. It was found that p38alpha is essential for lung function in both neonatal and adult mice. Increased proliferation and impaired differentiation are the hallmarks of p38alpha-deficient cells. Moreover, mice deficient in p38alpha are prone to cancer development using carcinogen or oncogene-induced cancer models. p38alpha 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.