Functional Interaction of E1AF and Sp1 in Glioma Invasion

Abstract

Transcription factor E1AF is widely known to play critical roles in tumor metastasis via directly binding to the promoters of genes involved in tumor migration and invasion. Here, we report for the first time E1AF as a novel binding partner for ubiquitously expressed Sp1 transcription factor. E1AF forms a complex with Sp1, contributes to Sp1 phosphorylation and transcriptional activity, and functions as a mediator between epidermal growth factor and Sp1 phosphorylation and activity. Sp1 functions as a carrier bringing E1AF to the promoter region, thus activating transcription of glioma-related gene for β1,4-galactosyltransferase V (GalT V; EC 2.4.1.38). Biologically, E1AF functions as a positive invasion regulator in glioma in cooperation with Sp1 partly via up-regulation of GalT V. This report describes a new mechanism of glioma invasion involving a cooperative effort between E1AF and Sp1 transcription factors.

This work was supported by 863 Program of China (grant 2001AA234031), National Natural Scientific Foundation of China (30330320 and 30700132), National Basic Research Program (2002CB512803), and a grant from the Development of Science and Technology of Shanghai (02DJ14002) and sponsored by Shanghai Educational Development Foundation.

We thank Guntram Suske (Marburg, Germany) for providing the PEVR2-Sp1 (human). We thank Liangfu Zhou (Nurosurgery, Huaashang Hospital, China) and Aiguo Shen (Laboratory of Neurobiology, Nantong University) for providing normal human brain tissues and glioma tissues.