Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TMT analysis of MOLM-13 cells treated with SJ001007095

ABSTRACT: Targeted Protein Degradation (TPD) encompasses two approaches that generate small molecules with similar proteasome-dependent mechanisms of action: Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues (MGs). Our goal is to develop novel MG approaches that exploit the E3 ubiquitin ligase Cereblon (CRBN) to degrade key oncogenic drivers in the leading causes of childhood cancer death: acute myeloid leukemia (AML). This project will identify new vulnerabilities and compounds that degrade hitherto undruggable transcription factors in high-risk acute leukemia (AL) and medulloblastoma (MB). Based on our preliminary data, we hypothesize that compound SJ001007095 targets AML cells independent of GSPT1 degradation. Our aims are to understand the mechanism by which compound SJ001007095 targets AML cells using TMT proteomic approach and identify proteins targeted by the compound SJ001007095 leading to their degradation and consequently AML cell death.

INSTRUMENT(S): Orbitrap Fusion, Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Yingxue Fu

LAB HEAD: Junmin Peng

PROVIDER: PXD045170 | Pride | 2023-12-01

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

TMT analysis of MOLM-13 cells treated with series 3 CK1a degraders

Project description:Targeted Protein Degradation (TPD) encompasses two approaches that generate small molecules with similar proteasome-dependent mechanisms of action: Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues (MGs). Our goal is to develop novel MG approaches that exploit the E3 ubiquitin ligase Cereblon (CRBN) to degrade key oncogenic drivers in the leading causes of childhood cancer death: acute myeloid leukemia (AML). This project will identify new vulnerabilities and compounds that degrade hitherto undruggable transcription factors in high-risk acute leukemia (AL) and medulloblastoma (MB). Based on our preliminary data, we hypothesize that these compounds target AML cells via CK1a degradation. Our aims are to understand the mechanism by which compounds SJ001041330, SJ001043149, and SJ001043301 target AML cells using TMT proteomic approach and confirm CK1a degradation by these compounds leading to AML cell death.

2023-12-01 | PXD045230 | Pride

Proteome profiling of MOLM-13 cells treated with proposed CK1α degraders

Project description:Targeted Protein Degradation (TPD) encompasses two approaches that generate small molecules with similar proteasome-dependent mechanisms of action: Proteolysis-Targeting Chimeras (PROTACs) and Molecular Glues (MGs). Our goal is to develop novel MG approaches that exploit the E3 ubiquitin ligase Cereblon (CRBN) to degrade key oncogenic drivers in the leading causes of childhood cancer death: acute myeloid leukemia (AML). This project will identify new vulnerabilities and compounds that degrade hitherto undruggable transcription factors in high-risk acute leukemia (AL) and medulloblastoma (MB). Based on our preliminary data, we hypothesize that each of these compounds (SJ001010039, SJ001010040, SJ001010041, SJ001010047, SJ001010050) degrades CK1α in this cell line and may degrade other proteins. Our aims are to confirm that CK1α is degraded by treatment with each of these compounds and to identify any additional proteins that are targeted for degradation by these compounds.

2023-12-01 | PXD045228 | Pride

RNA sequencing MOLM-13 cells treated with the UBE2N inhibitor UC-764864 or DMSO control

Project description:Dysregulation of innate immune and inflammatory signaling pathways is implicated in various hematologic malignancies. Yet, these pathways have not been systematically examined in acute myeloid leukemia (AML). We report that AML hematopoietic stem and progenitor cells (HSPCs) exhibit a high frequency of dysregulated innate immune-related and inflammatory pathways, referred to as oncogenic immune signaling states. Through gene expression analyses and functional genetic studies, we found that the ubiquitin (Ub) conjugating enzyme UBE2N is required for leukemic cell function in vitro and in vivo by maintaining oncogenicimmune signaling states. Using newly identified small molecule inhibitors of UBE2N as chemical probes, we further revealed the therapeutic efficacy of interfering with UBE2N Ub-conjugating function by preventing ubiquitination of multiple innate immune- and inflammatory-related substrates in AML. Inhibition of UBE2N catalytic function in AML disrupted oncogenic immune signaling by promoting cell death of leukemic HSPCs while sparing healthy cells. Moreover, baseline oncogenic immune signaling states in discrete subsets of primary AML patients exhibited a selective dependency on UBE2N catalytic function. Our study reveals that interfering with UBE2N function abrogates leukemic HSPCs and underscores the dependency of AML cells on UBE2N-dependent oncogenic immune signaling states

2022-09-30 | GSE184889 | GEO

RNA sequencing of MOLM-13 cells transduced with lentivirally expressed UBE2N or control short hairpin RNAs

Project description:Dysregulation of innate immune and inflammatory signaling pathways is implicated in various hematologic malignancies. Yet, these pathways have not been systematically examined in acute myeloid leukemia (AML). We report that AML hematopoietic stem and progenitor cells (HSPCs) exhibit a high frequency of dysregulated innate immune-related and inflammatory pathways, referred to as oncogenic immune signaling states. Through gene expression analyses and functional genetic studies, we found that the ubiquitin (Ub) conjugating enzyme UBE2N is required for leukemic cell function in vitro and in vivo by maintaining oncogenic immune signaling states. Using newly identified small molecule inhibitors of UBE2N as chemical probes, we further revealed the therapeutic efficacy of interfering with UBE2N Ub-conjugating function by preventing ubiquitination of multiple innate immune- and inflammatory-related substrates in AML. Inhibition of UBE2N catalytic function in AML disrupted oncogenic immune signaling by promoting cell death of leukemic HSPCs while sparing healthy cells. Moreover, baseline oncogenic immune signaling states in discrete subsets of primary AML patients exhibited a selective dependency on UBE2N catalytic function. Our study reveals that interfering with UBE2N function abrogates leukemic HSPCs and underscores the dependency of AML cells on UBE2N-dependent oncogenic immune signaling states

2022-09-30 | GSE184852 | GEO

Global Proteomic Profiling of Pediatric AML: A Pilot Study

Project description:Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics.

2023-09-26 | PXD043982 | Pride

Mitochondrial Fission 1 (FIS1) knockdown effect on the transcriptome of leukemia cell line MOLM-13 cells

Project description:To explore the function of Mitochondrial Fission 1 (FIS1) in acute myeloid leukemia (AML), we used shRNA to knock down the expression of FIS1 in leukemia cell line MOLM-13 cells and performed RNA-seq experiments to profile transcriptional changes upon FIS1 depletion.

2018-06-01 | GSE114111 | GEO

ChIP-seq analysis of H3K4me3, H3K9me3 and MPHOSPH8 in MOLM-13 cells

Project description:Human cancers including acute myeloid leukemia (AML) hijack epigenetic machinery to drive malignant self-renewal, whereas dysregulated epigenetic states also create selective and targetable liabilities. We performed domain-based CRISPR/Cas9 screens of human chromatin regulators and identified MPHOSPH8 (or MPP8), a component of the HUSH complex and repressor of LINE-1 retrotransposons, as a selective epigenetic dependency of AML cells. While dispensable for normal hematopoiesis, MPP8 loss inhibited AML initiation and maintenance by reactivating LINE-1 retrotransposons. Activation of endogenous or ectopic LINE-1 photocopied MPP8 loss, whereas blocking LINE-1 retrotransposition abrogated MPP8-deficiency-induced phenotypes. Reactivated LINE-1 retrotransposition increased DNA damage, activated cyclin-dependent kinase inhibitor p21 (or CDKN1A), and induced AML differentiation. Enhanced L1 suppression in AML stem cells is associated with therapy resistance and poor prognosis. Hence, while retrotransposons are historically recognized as sources of genetic instability and somatic mutations, we uncover an unexpected role for HUSH/MPP8 in promoting cancer by suppressing genomic transposable elements.

2021-02-01 | GSE150981 | GEO

A Pyrazolo[3,4-d]Pyrimidine compound (a Fyn inhibitor) induces apoptosis and cell death in Large Granular Lymphocyte Leukemia cells

Project description:KHYG1 cell line (NK leukemia) were treated with a new compound, a pyrazolo[3,4-d]Pyrimidine. This compound induces apoptosis and cell death in this cell line. The mechanisms of apoptosis and cell death were investigated. A gene expression profile was used as support.

2016-10-03 | E-MTAB-4536 | biostudies-arrayexpress

RNA-seq analysis of transcriptomic changes in WT and MPHOSPH8 KO MOLM-13 leukemia cells

2021-02-01 | GSE150982 | GEO

Unleashing cell-intrinsic inflammation as a strategy to kill AML blasts [RNA-seq]

Project description:Leukemic blasts are immune cells gone awry. We hypothesized that dysregulation of inflammatory pathways contributes to the maintenance of their leukemic state and can be exploited as a cell-intrinsic, self-directed immunotherapy. To this end, we applied genome-wide screens to discover genetic vulnerabilities in acute myeloid leukemia (AML) cells that are also implicated in inflammatory pathways. We identified the immune modulator interferon regulatory factor 2 binding protein 2 (IRF2BP2) as a selective dependency in AML. We validated AML cell dependency on IRF2BP2 with genetic and protein degradation approaches in vitro and genetically in vivo. Chromatin and global gene expression studies demonstrated that IRF2BP2 represses IL1B/TNFA signaling via NF-KB, and IRF2BP2 perturbation results in an acute inflammatory state leading to AML cell death. These findings elucidate a hitherto unexplored AML dependency, reveal cell-intrinsic inflammatory signaling as a mechanism priming leukemic blasts for regulated cell death, and establish IRF2BP2-mediated transcriptional repression as a mechanism for blast survival.

2022-05-23 | GSE168648 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data