title: E2 ligase dRad6 regulates DMP53 turnover in Drosophila.
abstract: The turnover of tumor suppressor p53 is critical for its role in various cellular events. However, the pathway that regulates the turnover of the Drosophila melanogaster DMP53 is largely unknown. Here, we provide evidence for the first time that the E2 ligase, Drosophila homolog of Rad6 (dRad6/Dhr6), plays an important role in the regulation of DMP53 turnover. Depletion of dRad6 results in DMP53 accumulation, whereas overexpression of dRad6 causes enhanced DMP53 degradation. We show that dRad6 specifically interacts with DMP53 at the transcriptional activation domain and regulates DMP53 ubiquitination. Loss of dRad6 function in transgenic flies leads to lethalities and altered morphogenesis. The dRad6-induced defects in cell proliferation and apoptosis are found to be DMP53-dependent. The loss of dRad6 induces an accumulation of DMP53 that enhances the activation of apoptotic genes and leads to apoptosis in the presence of stress stimuli. In contrast to that, the E3 ligase is the primary factor that regulates p53 turnover in mammals, and this work demonstrates that the E2 ligase dRad6 is critical for the control of DMP53 degradation in Drosophila.
authors.affiliation: Institute of Epigenetics and Cancer Research, Medical Science Building C-315, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wei
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Lv
authors.forename: Da-Liang
authors.initials: DL
authors.lastname: Wang
authors.forename: Fang-Lin
authors.initials: FL
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D009024:Morphogenesis / Q000502:physiology; D017434:Protein Structure, Tertiary; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D029721:Drosophila Proteins; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila; C489286:Ubc6 protein, Drosophila; D044763:Ubiquitin-Conjugating Enzymes