Deubiquitinase USP48 promotes ATRA-induced granulocytic differentiation of acute promyelocytic leukemia cells

  • Authors:
    • Lianlian Li
    • Yong Wang
    • Xiaoyu Zhang
    • Guanhua Song
    • Qiang Guo
    • Zhiyong Zhang
    • Yutao Diao
    • Haipeng Yin
    • Hongyan Liu
    • Guosheng Jiang
  • View Affiliations

  • Published online on: June 13, 2018     https://doi.org/10.3892/ijo.2018.4440
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Abstract

All-trans retinoic acid (ATRA) has been used for the treatment of acute promyelocytic leukemia (APL). However, its molecular mechanisms of action are unclear. Ubiquitin-specific protease 48 (USP48) is a deubiquitinase enzyme that can post-translationally remove ubiquitin molecules from substrates. In the present study, the role of USP48 in ATRA-induced differentiation of APL cells was studied. The expression of USP48 decreased following ATRA treatment. Functionally, overexpression of USP48 using electroporation-mediated delivery inhibited the proliferation of APL cells and promoted ATRA-mediated differentiation. The inverse observations were made upon siRNA-mediated knockdown of USP48. Furthermore, the expression of USP48 was increased in the nucleus upon ATRA exposure for ≤24 h, suggesting that USP48 was translocated into the nucleus. Interestingly, regulation of p65, a substrate of USP48, did not contribute to the downstream mechanism of ATRA-induced differentiation of APL cells. In addition, upstream mechanistic studies demonstrated that the expression of USP48 was regulated by microRNA-301a-3p. In conclusion, the present study highlights the function of USP48 in the ATRA-induced granulocytic differentiation of APL cells and provides a theoretical basis for identifying novel targets for differentiation therapy of APL.

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APA
Li, L., Wang, Y., Zhang, X., Song, G., Guo, Q., Zhang, Z. ... Jiang, G. (1899). Deubiquitinase USP48 promotes ATRA-induced granulocytic differentiation of acute promyelocytic leukemia cells. International Journal of Oncology, 0, 0-0. https://doi.org/10.3892/ijo.2018.4440
MLA
Li, L., Wang, Y., Zhang, X., Song, G., Guo, Q., Zhang, Z., Diao, Y., Yin, H., Liu, H., Jiang, G."Deubiquitinase USP48 promotes ATRA-induced granulocytic differentiation of acute promyelocytic leukemia cells". International Journal of Oncology 0.0 (1899): 0-0.
Chicago
Li, L., Wang, Y., Zhang, X., Song, G., Guo, Q., Zhang, Z., Diao, Y., Yin, H., Liu, H., Jiang, G."Deubiquitinase USP48 promotes ATRA-induced granulocytic differentiation of acute promyelocytic leukemia cells". International Journal of Oncology 0, no. 0 (1899): 0-0. https://doi.org/10.3892/ijo.2018.4440