Arai Honoka, Maki Kazuhiro, Waga Kazuo, Sasaki Ko, Nakamura Yuichi, Imai Yoichi, Kurokawa Mineo, Hirai Hisamaru, Mitani Kinuko
Department of Hematology, Dokkyo University School of Medicine, 321-0293, Tochigi, Japan.
Biochem Biophys Res Commun. 2002 Nov 22;299(1):116-25. doi: 10.1016/s0006-291x(02)02588-3.
TEL is a nuclear phosphoprotein that belongs to a member of the ETS family transcription factors. TEL acts as a tumor suppressor and is essential for establishing hematopoiesis in neonatal bone marrow. Because TEL possesses multiple putative mitogen-activated protein (MAP) kinase phosphorylation sites, we here investigated functional regulation of TEL via stress signaling pathways. We showed that TEL becomes phosphorylated in vivo by activated p38 but not by JNK1. The constitutive and inducible phosphorylation sites were found to be Ser(22) and Ser(257), respectively. TEL bound to p38 and was directly phosphorylated in vitro by p38. In vivo p38-dependent phosphorylation reduced trans-repressional abilities of TEL through ETS-binding consensus site. These data indicate that TEL's functions are potentially regulated by p38 which is activated by various kinds of stresses. TEL could be a constituent downstream of the specific MAP kinase in the signal transduction system.
TEL是一种核磷蛋白，属于ETS家族转录因子成员。TEL作为一种肿瘤抑制因子，对新生儿骨髓中造血作用的建立至关重要。由于TEL具有多个假定的丝裂原活化蛋白（MAP）激酶磷酸化位点，我们在此研究了通过应激信号通路对TEL的功能调控。我们发现，TEL在体内被激活的p38磷酸化，但不被JNK1磷酸化。组成型和诱导型磷酸化位点分别为Ser(22)和Ser(257)。TEL与p38结合，并在体外被p38直接磷酸化。体内p38依赖的磷酸化通过ETS结合共有位点降低了TEL的反式抑制能力。这些数据表明，TEL的功能可能受p38调控，而p38可被各种应激激活。TEL可能是信号转导系统中特定MAP激酶的下游成分。
