MYB: An old oncoprotein with new roles

Abstract

Over the last decade, the c-myb gene and its protein product, Myb, have undergone extensive examination and manipulation in hemopoietic tissues. Although it is rarely disputed that, as a transcription factor, Myb regulates cell cycling, proliferation and differentiation, identification of genes directly controlled by Myb has been surprisingly difficult. More recently, genes with promoter regions that contain Myb recognition sequences have been identified, but a direct proliferative response to Myb via these 'target genes' has yet to be demonstrated. Mutagenesis studies have defined domains of the protein which influence its transcriptional activity and transforming potential; however how the molecule interacts with itself and with other cellular factors is only beginning to be understood. A broader examination of c-myb expression in normal and malignant tissues suggests an analogous role for Myb in proliferation, differentiation and transformation of non-hemopoietic tissues.

The human neuroendocrine thyrotropin-releasing hormone receptor promoter is activated by the haematopoietic transcription factor c-Myb

“…Consistent with this, mice with a mutant TSH receptor (hyt/hyt mice) were found to have a selectively impaired intestinal T-cell repertoire [46]. It would have been interesting to study whether the high expression of c-Myb in the intestine [47,48] also plays a role in controlling expression of TRHR in this organ. Another attractive line of investigation would have been to study links between mutations in the gene for the TRHR and impaired immune function.…”

Function Search in a Large Transcription Factor Gene Family in Arabidopsis: Assessing the Potential of Reverse Genetics to Identify Insertional Mutations in R2R3 MYB Genes

“…Subsequently identified members of the MYB gene family represent all major eukaryotic groups (Rosinski and Atchley, 1998). In animals and yeast, the number of identified MYB genes is small (Thompson and Ramsay, 1995;Rosinski and Atchley, 1998), but a much larger number of MYB genes has been identified in plants (Martin and Paz-Ares, 1997). Although some of these plant MYB genes contain only a single repeat (Baranowskij et al, 1994;Kirik and Bäumlein, 1996;Feldbrügge et al, 1997), the largest group is the R2R3 class, containing two imperfect MYB-like repeats in their DNA binding domains (Jackson et al, 1991;Avila et al, 1993;Lin et al, 1996;Romero et al, 1998).…”

“…Whereas many animal MYB genes have been found to function in the control of cell proliferation and differentiation (Thompson and Ramsay, 1995), the functions of MYB genes in plants appear to be far more diverse and, with the exception of a few intensely studied examples, remain much less clear. Some plant R2R3 MYB genes are known to regulate secondary metabolism, particularly in the phenylpropanoid pathway (Paz-Ares, 1987;Grotewold et al, 1994;Sablowski et al, 1994;Moyano et al, 1996;Tamagnone et al, 1998) and tryptophan biosynthesis (Bender and Fink, 1998).…”

“…Although some of these plant MYB genes contain only a single repeat (Baranowskij et al, 1994;Kirik and Bäumlein, 1996;Feldbrügge et al, 1997), the largest group is the R2R3 class, containing two imperfect MYB-like repeats in their DNA binding domains (Jackson et al, 1991;Avila et al, 1993;Lin et al, 1996;Romero et al, 1998). To date, Ͼ 92 R2R3-type MYB genes have been characterized in Arabidopsis (Kranz et al, 1998).Whereas many animal MYB genes have been found to function in the control of cell proliferation and differentiation (Thompson and Ramsay, 1995), the functions of MYB genes in plants appear to be far more diverse and, with the exception of a few intensely studied examples, remain much less clear. Some plant R2R3 MYB genes are known to regulate secondary metabolism, particularly in the phenylpropanoid pathway (Paz-Ares, 1987;Grotewold et al, 1994;Sablowski et al, 1994;Moyano et al, 1996;Tamagnone et al, 1998) and tryptophan biosynthesis (Bender and Fink, 1998).…”

Inhibition of human hematopoietic tumor formation by targeting a repressor Myb-KRAB to DNA

“…C-Myb is essential for proliferation of immature hematopoietic cells and is highly expressed during the early stages of hematopoietic differentiation and in various hematopoietic malignancies. 1,2 The structure of c-Myb consists of three domains, an amino terminal DNA binding domain (DBD) comprising three repeats of 21 amino acids, a highly acidic transactivating domain, and two negatively regulating domains, which are absent in the viral v-Myb. 3 V-and c-Myb bind to their specific DNA binding sequence and transactivate cellular target genes such as the promyelocytic-specific mim-1 gene.…”