2001.The chicken Pdcd4 gene is regulated by v-Myb.pdf

The chicken Pdcd4 gene is regulated by v-Myb Ursula Schlichter1, Oliver Burk1,2, Susanne Worpenberg1,3 and Karl-Heinz Klempnauer*,1 1Institut fuèr Biochemie, Westfaèlische-Wilhelms-Universitaèt Muènster, Wilhelm-Klemm-Str. 2, D-48149 Muènster, Germany The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the ability of avian myeloblastosis virus (AMV) to transform myelo- monocytic cells. v-Myb is thought to disrupt the di?erentiation of myelomonocytic cells by a?ecting the expression of speci?c target genes. To identify such genes we have analysed the gene expression in a myelomonocytic chicken cell line that carries an estrogen inducible version of v-Myb by di?erential display. Here we describe the identi?cation of the chicken homolog of the mouse Pdcd4 gene as a novel v-Myb target gene. Pdcd4 is also known as MA-3, TIS and H731 and has recently been shown to suppress the transformation of epidermal cells by tumor promoters. Our results provide the ?rst evidence that v-Myb directly regulates the expression of a potential tumor suppressor gene. Oncogene (2001) 20, 231 ± 239. Keywords: v-myb oncogene; target gene; di?erential display; Pdcd4 Introduction The v-myb oncogene of avian myeloblastosis virus (AMV) encodes a transcription factor (referred to as v- Myb) which is responsible for the ability of AMV to transform myelomonocytic cells in vivo and in vitro (for review see: Ness, 1996; Lipsick and Wang, 1999). v- Myb is an altered version of c-Myb, the protein encoded by the chicken c-myb gene. Nucleotide sequences from both ends of the c-myb coding region have been lost during retroviral transduction of the oncogene; in addition v-myb harbors several point mutations which result in a number of aminoacid replacements (Klempnauer et al., 1982, 1983). A large body of evidence indicates that c-myb is essential for the development of the hematopoietic system and plays an important role as a switch that directs hematopoie- tic prog