Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth and proliferation during Drosophila development
Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth and proliferation during Drosophila development
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DOI：
10.1073/pnas.0408945102
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发表时间：
2005-08-16
影响因子：
11.1
通讯作者：
Gallant, P
中科院分区：
文献类型：
--
作者：
Bellosta, P;Hulf, T;Gallant, P
转录因子dMyc是脊椎动物c-myc原癌基因在果蝇中唯一的同源基因，是正常发育过程中生长和细胞周期进程的中央调节因子。我们通过分析dMyc与可能的转录辅助因子Tip48/Reptin(REPT)和Tip49/Pontin(Pont)的相互作用，研究了dMyc功能的分子基础。我们证明了REPT和Pont在进化过程中保留了与Myc结合的能力。所有这三种蛋白质都是体内组织生长所必需的，因为突变了dmyc、pont或rept的有丝分裂克隆会受到细胞竞争的影响。最重要的是，Pont与dmyc表现出很强的显性遗传交互作用，这表现在成年动物的发育持续时间、存活率和大小上，特别是眼睛。这些作用的分子基础可能是dMyc：Pont复合体对某些靶基因的抑制，如MFAs。这些发现表明，dMyc：Pont复合体在正常发育过程中对细胞的生长和增殖起着重要的控制作用。
The transcription factor dMyc is the sole Drosophila ortholog of the vertebrate c-myc protooncogenes and a central regulator of growth and cell-cycle progression during normal development. We have investigated the molecular basis of dMyc function by analyzing its interaction with the putative transcriptional cofactors Tip48/Reptin (Rept) and Tip49/Pontin (Pont). We demonstrate that Rept and Pont have conserved their ability to bind to Myc during evolution. All three proteins are required for tissue growth in vivo, because mitotic clones mutant for either dmyc, pont, or rept suffer from cell competition. Most importantly, pont shows a strong dominant genetic interaction with dmyc that is manifested in the duration of development, rates of survival and size of the adult animal and, in particular, of the eye. The molecular basis for these effects may be found in the repression of certain target genes, such as mfas, by dMyc:Pont complexes. These findings indicate that dMyc:Pont complexes play an essential role in the control of cellular growth and proliferation during normal development.