40 research outputs found
WT1 and its transcriptional cofactor BASP1 redirect the differentiation pathway of an established blood cell line
High frequencies of simultaneous FLT3-ITD, WT1 and KIT mutations in hematological malignancies with NUP98-fusion genes
Evaluation of WT1 expression in bone marrow vs peripheral blood samples of children with acute myeloid leukemia—impact on minimal residual disease detection
Homology modeling and molecular dynamics studies of Wilms’ tumor gene 1 frameshift mutations in exon 7
Computational study of self-centering buckling-restrained braced frame seismic performance
Influence of post-onset stiffness on seismic responses of BRBFs with gap-supported protections
Use of CD137 to study the full repertoire of CD8+ T cells without the need to know epitope specificities
Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia
The Wilms' Tumor Suppressor Protein WT1 Is Processed by the Serine Protease HtrA2/Omi
The Wilms' tumor suppressor protein WT1 functions as a transcriptional regulator of genes controlling growth, apoptosis, and differentiation. It has become clear that WT1 can act as an oncogene in many tumors, primarily through the inhibition of apoptosis. Here, we identify the serine protease HtrA2 as a WT1 binding partner and find that it cleaves WT1 at multiple sites following the treatment of cells with cytotoxic drugs. Ablation of HtrA2 activity either by chemical inhibitor or by siRNA prevents the proteolysis of WT1 under apoptotic conditions. Moreover, the apoptosis-dependent cleavage of WT1 is defective in HtrA2 knockout cells. Proteolysis of WT1 by HtrA2 causes the removal of WT1 from its binding sites at gene promoters, leading to alterations in gene regulation that enhance apoptosis. Our findings provide insights into the function of HtrA2 in the regulation of apoptosis and the oncogenic activities of WT1