May 25, 2021 · Here we demonstrate that cancer-associated frameshift mutations in ASXL1, which were originally proposed to act as destabilizing loss-of-function mutations, in fact encode stable truncated...

Jul 16, 2018 · In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promoting myeloid leukaemogenesis. BAP1 expression results in...

Jul 16, 2018 · In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promoting myeloid leukaemogenesis. BAP1 expression results in increased monoubiquitination of ASXL1-MT, which in turn increases the catalytic function of BAP1.

Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Oct 9, 2012 · Here we discuss new evidence for a BAP1-independent function of ASXL1 in regulating histone H3 lysine 27 methylation through interactions with the Polycomb-repressive complex 2 (PRC2).

This study represents a breakthrough in our understanding of the molecular mechanisms of ASXL1 mutations in leukemia pathogenesis and identifies small-molecular catalytic inhibitors of BAP1 as a potential targeted therapy for leukemia.

Dec 8, 2017 · In the present study, we found a mutually reinforcing effect between a C-terminally truncating ASXL1 mutant (ASXL1-MT) and the histone H2A deubiquitinase BAP1. Biochemical analyses revealed that BAP1 stabilized ASXL1-MT and induced its monoubiquitination at …

Jul 16, 2018 · In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promoting myeloid leukaemogenesis. BAP1 expression results in increased monoubiquitination of ASXL1-MT, which in turn increases the catalytic function of BAP1.

Jul 18, 2020 · Phenotypically, mutant ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcriptional nexus and downregulates TXNIP, VHL, and SOCS1/2, and consequently promotes glucose metabolism and enhances oncogenic HIF-1α and JAK-STAT3 signaling pathways known to be altered in hematological malignancies.

Using CRISPR/Cas9 knockout and overexpression technology in mouse trophoblast stem cells, here we demonstrate that the downregulation of BAP1 protein is essential to trigger epithelial-mesenchymal transition (EMT) during trophoblast differentiation associated with a …