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• W2150622093 startingPage "e23389" @default.
• W2150622093 abstract "Cdc20-anaphase promoting complex/cyclosome (Cdc20-APC/C) E3 ubiquitin ligase activity is essential for orderly mitotic progression. The deubiqituinase USP44 was identified as a key regulator of APC/C and has been proposed to suppress Cdc20-APC/C activity by maintaining its association with the inhibitory protein Mad2 until all chromosomes are properly attached to the mitotic spindle. However, this notion has been challenged by data in which a lysine-less mutant of Cdc20 leads to premature anaphase, suggesting that it's ubiquitination is not required for APC/C activation. To further evaluate its role in checkpoint function and chromosome instability, we studied the consequences of over-expression of mouse Usp44 in non-transformed murine embryonic fibroblasts. Here we show that cells with high Usp44 are prone to chromosome segregation errors and aneuploidization. We find that high Usp44 promotes association of Mad2 with Cdc20 and reinforces the mitotic checkpoint. Surprisingly, the APC/C-Cdc20 substrate cyclin B1 is stabilized in G2 when Usp44 is over-expressed, but is degraded with normal kinetics once cells enter mitosis. Furthermore, we show that USP44 expression is elevated in subset of T-cell leukemias. These data are consistent with an important role for USP44 in regulating Cdc20-APC/C activity and suggest that high levels of this enzyme may contribute to the pathogenesis of T-ALL." @default.
• W2150622093 created "2016-06-24" @default.
• W2150622093 creator A5027265757 @default.
• W2150622093 creator A5042973046 @default.
• W2150622093 creator A5072542382 @default.
• W2150622093 date "2011-08-11" @default.
• W2150622093 modified "2023-09-26" @default.
• W2150622093 title "Overexpression of Ubiquitin Specific Protease 44 (USP44) Induces Chromosomal Instability and Is Frequently Observed in Human T-Cell Leukemia" @default.
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• W2150622093 doi "https://doi.org/10.1371/journal.pone.0023389" @default.
• W2150622093 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3154946" @default.
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• W2150622093 hasPublicationYear "2011" @default.
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