【摘 要】
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RPL41 is a small basic ribosomal protein with 25 amino acids.A functional screening revealed that downregulation of RPL41 induced cell transformation in NIH3T3 cells; deletions and downregulation of R
【机 构】
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Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston USA
【出 处】
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BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
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RPL41 is a small basic ribosomal protein with 25 amino acids.A functional screening revealed that downregulation of RPL41 induced cell transformation in NIH3T3 cells; deletions and downregulation of RPL41 are frequently detected in tumors, suggesting a tumor suppression role for RPL41.By GST-RPL41 pull down followed with mass spectrum analysis, DNA-dependent protein kinase (DNA-PK) was identifed as one of the RPL41 associated proteins.The interaction between RPLA 1 and DNA-PK dramatically increased the autophosphorylation of DNA-PK catalytic subunit (DNA-PKes) and its kinase activity.On the other hand, cells with RPL41 down regulation were defective in DNA-PK kinase activation.RPL41 localized in nucleoti (highly), nuclei (medium), and cytoplasm (low-level).A synthetic RPL41 peptide was able to penetrate cell membrane, localized rapidly to its physiologic cellular compartments, induced autophopharylation of cellular DNA-PKcs, and caused a DNA-PK dependent activation of death-associated protein kinase (DAPK) and autophagy.Administration of synthetic RPL41 peptide in mice with tumors significantly inhibited tumor growth, suggesting that RPL41, being chemically synthesizable and self cell-penetrating, may have potential in cancer therapies.
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