Sox4 cooperates with CREB in myeloid transformation

Salemiz Sandoval, Christina Kraus, Er Chieh Cho, Michelle Cho, Juraj Bies, Elena Manara, Benedetta Accordi, Elliot M. Landaw, Linda Wolff, Martina Pigazzi, Kathleen M. Sakamoto

研究成果: 雜誌貢獻文章同行評審

35 引文 斯高帕斯(Scopus)

摘要

The cAMP response element-binding protein (CREB) is a nuclear transcription factor that is critical for normal and neoplastic hematopoiesis. Previous studies have demonstrated that CREB is a proto-oncogene whose overexpression promotes cellular proliferation in hematopoietic cells. Transgenic mice that overexpress CREB in myeloid cells develop a myeloproliferative disease with splenomegaly and aberrant myelopoiesis. However, CREB overexpressing mice do not spontaneously develop acute myeloid leukemia. In this study, we used retroviral insertional mutagenesis to identify genes that accelerate leukemia in CREB transgenic mice. Our mutagenesis screen identified several integration sites, including oncogenes Gfi1, Myb, and Ras. The Sox4 transcription factor was identified by our screen as a gene that cooperates with CREB in myeloid leukemogenesis. We show that the transduction of CREB transgenic mouse bone marrow cells with a Sox4 retrovirus increases survival and selfrenewal of cells in vitro. Furthermore, leukemic blasts from the majority of acute myeloid leukemia patients have higher CREB, phosphorylated CREB, and Sox 4 protein expression. Sox4 transduction of mouse bone marrow cells results in increased expression of CREB target genes. We also demonstrate that CREB is a direct target of Sox4 by chromatin immunoprecipitation assays. These results indicate that Sox4 and CREBcooperate and contribute to increased proliferation of hematopoietic progenitor cells.

原文英語
頁(從 - 到)155-165
頁數11
期刊Blood
120
發行號1
DOIs
出版狀態已發佈 - 七月 5 2012
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 免疫學
  • 血液學
  • 細胞生物學

指紋

深入研究「Sox4 cooperates with CREB in myeloid transformation」主題。共同形成了獨特的指紋。

引用此