tailieunhanh - Báo cáo sinh học: "Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila. | Gluderer et al. Journal of Biology 2010 9 9 http content 9 1 9 Journal of Biology RESEARCH Open Access Madm Mlf1 adapter molecule cooperates with Bunched A to promote growth in Drosophila Silvia Gluderer1 Erich Brunner2 Markus Germann3 Virginija Jovaisaite1 Changqing Li4 5 Cyrill A Rentsch3 6 Ernst Hafen1 and Hugo Stocker 1 See minireview at http content 9 1 8 Abstract Background The TSC-22 domain family TSC22DF consists of putative transcription factors harboring a DNA-binding TSC-box and an adjacent leucine zipper at their carboxyl termini. Both short and long TSC22DF isoforms are conserved from flies to humans. Whereas the short isoforms include the tumor suppressor TSC-22 Transforming growth factor-pi stimulated clone-22 the long isoforms are largely uncharacterized. In Drosophila the long isoform Bunched A BunA acts as a growth promoter but how BunA controls growth has remained obscure. Results In order to test for functional conservation among TSC22DF members we expressed the human TSC22DF proteins in the fly and found that all long isoforms can replace BunA function. Furthermore we combined a proteomics-based approach with a genetic screen to identify proteins that interact with BunA. Madm Mlfi adapter molecule physically associates with BunA via a conserved motif that is only contained in long TSC22DF proteins. Moreover DrosophilaMadm acts as a growth-promoting gene that displays growth phenotypes strikingly similar to bunA phenotypes. When overexpressed Madm and BunA synergize to increase organ growth. Conclusions The growth-promoting potential of long TSC22DF proteins is evolutionarily conserved. Furthermore we provide biochemical and genetic evidence for a growth-regulating complex involving the long TSC22DF protein BunA and the adapter molecule Madm. Background A prevalent model of carcinogenesis suggests that sequential activation of oncogenes and inactivation of tumor suppressor genes occur in a multistep process leading to deviant