Transcriptomics

Dataset Information

0

Systematic evaluation of GAPs and GEFs identifies ARHGAP45 as a targetable leukemia-specific RhoGAP dependency


ABSTRACT: GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs) function as negative and positive regulators of small GTPases, respectively, and play key roles in cell fate determination. The aberrant function of GAPs and GEFs has long been implicated in cancer development but their vast number and potential redundancy have hindered comprehensive understanding of their roles. Here we performed functional genetic screens of GAPs and GEFs in primary AML specimens to uncover an unexpected and selective role for ARHGAP45 in AML. Depletion of ARHGAP45 impedes AML growth without affecting normal human CD34+ cells in vivo. Epistasis screens revealed RhoA as the major substrate of ARHGAP45 and that depletion of the Rho GTPase CDC42 synergized with ARHGAP45 deletion. Consistent with this, pharmacologic CDC42 inhibition enhanced the effect of ARHGAP45 deletion. ARHGAP45 gives rise to a minor histocompatibility antigen (termed HA-1), which can be recognized by antigen-specific T cells. CDC42 inhibition not only sensitized AML cells to ARHGAP45 inhibition but also promoted the activity of HA-1 antigen-specific T cells by upregulating ARHGAP45-derived epitope in AML cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273164 | GEO | 2024/07/26

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-09-02 | BIOMD0000000899 | BioModels
2019-07-17 | PXD013668 | Pride
2020-06-20 | GSE152836 | GEO
2022-02-22 | PXD006326 | Pride
2021-02-04 | PXD018016 | Pride
2024-07-22 | GSE251817 | GEO
| PRJNA1140357 | ENA
2012-04-17 | E-GEOD-35405 | biostudies-arrayexpress
2012-04-17 | GSE35405 | GEO
| PRJNA243869 | ENA