IndraLab

Statements

USP15 binds TIFAB. 13 / 13
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"Their studies indicate that deregulation of the TIFAB-USP15 complex, as observed in del(5q) myelodysplasia or MLL-rearranged leukemia, modulates p53 activity and has critical functional consequences for stressed and malignant hematopoietic cells."
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"TIFAB binds to the catalytic domain of USP15 resulting in improved activities such as deubiquitination of MDM2 (a Ub E3 ligase of p53) [ xref ]."
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"TIFAB forms a complex with USP15, increasing the rate of USP15 deubiquitination and regulating p53 signaling in malignant hematopoietic cells [ xref ]."
32354135
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"Since TIFAB regulates USP15 DUB activity and substrates implicated in p53 activation, we hypothesized that deregulation of the TIFAB-USP15 complex, such as by genetic deletion of TIFAB, would sensitize hematopoietic cells to a variety of cellular stressors."
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"TIFAB Binds the Catalytic Domain of USP15 and Increases Its Rate of Deubiquitination."
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"Since we observed that TIFAB binds the catalytic domain of USP15 and the binding of TIFAB to USP15 is affected by the deubiquitinase activity of USP15, we next sought to determine whether TIFAB binding affects USP15 deubiquitinating activity."
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"TIFAB binds USP15 mutants that harbor residues 1–583 and 470–981 ( xref )."
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"Our data revealed that TIFAB binds USP15 and may impact cellular stress responses related to p53-dependent signaling pathways."
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"Our data suggest that the TIFAB-USP15 complex is important for maintaining leukemic progenitor function."
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"Given that the TIFAB-USP15 axis suppresses p53-mediated stress in hematopoietic cells, we sought to determine whether this pathway was relevant in AML."
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"We hypothesized that high expression of TIFAB could indicate a potential functional dependency of leukemic cells on the TIFAB-USP15 complex as a means of inhibiting tumor-suppressive p53 activity."
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"Our previous study in hematopoietic cells uncovered a TIFAB-USP15 complex that affects p53 signaling and cellular stress responses [ xref , xref ], indicating that USP15 might have several important roles in leukemic progenitors."
34465865
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"In summary, our data support a model in which deregulation of the TIFAB-USP15 complex, such as in del(5q) MDS or MLL-rearranged leukemia, modulates p53 activity and has critical functional consequences for stressed and malignant hematopoietic cells."
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