ISSN: 1449-1907International Journal of Medical Sciences
Global reach, higher impact
Int J Med Sci 2022; 19(14):2022-2032. doi:10.7150/ijms.74535 This issue Cite
Research Paper
USP44 accelerates the growth of T-cell acute lymphoblastic leukemia through interacting with WDR5 and repressing its ubiquitination
The Second Department of Pediatric Hematology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a common hematologic malignancy. Based on the data from GSE66638 and GSE141140, T-ALL patients depicted a higher USP44 level. However, its role in T-ALL is still unclear. In the present study, we investigated the role of USP44 in T-ALL growth. USP44 overexpression elevated the proliferation of CCRF-CEM cells, while USP44 knockdown suppressed the proliferation of Jurkat and MOLT-4 cells. In addition, USP44 accelerated the cell cycle progression, with boosted cyclinD and PCNA levels. However, USP44 knockdown induced apoptosis in Jurkat and MOLT-4 cells, with an upheaval among cleaved caspase-3 and PARP levels. Mechanistically, USP44 co-localized and interacted with WDR5, leading to the repression of its ubiquitination and degradation. Interestingly, WDR5 overexpression abolished the apoptosis induced by USP44 knockdown. Consistently, the in vivo study revealed that USP44 knockdown restricted the leukemic engraftments in the bone marrow and spleens and reduced the infiltration of T-ALL cells in the livers and lungs. In conclusion, this study indicated that USP44 enhanced the growth of T-ALL through interacting with WDR5 and repressing its ubiquitination. This study highlights the potential use of USP44 as a therapeutic target of T-ALL.
Keywords: T-cell acute lymphoblastic leukemia, USP44, WDR5, ubiquitination
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