Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Homolog-selective degradation as a strategy to probe the function of CDK6 in AML

ABSTRACT: Homolog-selective degradation as a strategy to probe the function of CDK6 in AML

PROVIDER: PRJNA477657 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR7416670.fastq.gz	Fastqsanger.gz
	SRR7416671.fastq.gz	Fastqsanger.gz
	SRR7416672.fastq.gz	Fastqsanger.gz
	SRR7416673.fastq.gz	Fastqsanger.gz
	SRR7416674.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Homolog-selective degradation as a strategy to probe the function of CDK6 in AML

Project description:The design of selective small-molecules is often stymied by similar ligand binding pockets. Here we report the first cyclin-dependent kinase 6 (CDK6) degrader, BSJ-03-123, that uses phthalimide-conjugation to exploit protein-interface determinants to achieve proteome-wide degradation selectivity. Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and coupling acute degradation with transcriptomics and phosphoproteomics enabled dynamic mapping of the immediate role of CDK6 in coordinating signaling and transcription.

2018-11-20 | GSE116187 | GEO

Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML.

Project description:The design of selective small molecules is often stymied by similar ligand binding pockets. Here, we report BSJ-03-123, a phthalimide-based degrader that exploits protein-interface determinants to achieve proteome-wide selectivity for the degradation of cyclin-dependent kinase 6 (CDK6). Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and transcriptomics and phosphoproteomics profiling of acute degradation of CDK6 enabled dynamic mapping of its immediate role in coordinating signaling and transcription.

| S-EPMC6444916 | biostudies-literature

CDK6 degradation is counteracted by p16INK4A and p18INK4C in AML

Project description:Cyclin-dependent kinase 6 (CDK6) represents a novel therapeutic target for the treatment of certain subtypes of acute myeloid leukemia (AML). CDK4/6 kinase inhibitors have been widely studied in many cancer types and their effects may be limited by primary and secondary resistance mechanisms. CDK4/6 degraders, which eliminate kinase dependent and kinase independent effects, have been suggested as alternative therapeutic option. We show that efficacy of the CDK6 specific protein degrader BSJ-03-123 varies among AML subtypes and depends on low expression of the INK4 proteins p16INK4A and p18INK4C. INK4 protein levels are significantly elevated in MLL-AF9+ compared to AML1-ETO+ cells, contributing to the different CDK6 degradation efficacy. We demonstrate that CDK6 complexes containing p16INK4A or p18INK4C are protected from BSJ-mediated degradation and that INK4 levels define the proliferative response to CDK6 degradation. These findings define INK4 proteins as predictive marker for CDK6 degradation – targeted therapies in AML.

2022-04-04 | PXD032216 | Pride

RNA-seq data from VavCre;Jak2+/+; Cdk6+/+, VavCre;Jak2V617F; Cdk6+/+, VavCre;Jak2V617F; Cdk6-/-, VavCre; Jak2+/+; Cdk6-/- murine bone marrow LSK cells and VavCre; Jak2V617F; Cdk6+/+ Palbociclib treated murine bone marrow LSK cells

Project description:We describe a critical role for Cdk6 in JAK2V617F+ MPN evolution. The absence of Cdk6 ameliorates clinical symptoms and prolongs survival of JAK2V617F fl/+ vav-Cre mice. The Cdk6 protein interferes with three hallmarks of disease: besides regulating malignant stem cell quiescence, it promotes NFkB signaling and contributes to cytokine production while inhibiting apoptosis. The treatment with palbociclib did not mirror these effects, showing that the functions of Cdk6 in MPN pathogenesis are largely kinase-independent.

2019-06-10 | GSE123401 | GEO

ChIP sequencing experiment of HA-tagged WT CDK6 or of a C-terminally truncated variant of CDK6 (CDK6 delta-C) in BCR-ABL1 expressing cell lines

Project description:The cell cycle kinase CDK6 interacts with a variety of proteins including cyclins and members of the INK4 and Cip/Kip families. These interactions are thought to involve primarily the N-lobe of the protein. Less is known about the role of the C-lobe for the function of CDK6. In this experiment we assessed the function of the C-lobe in CDK6's interaction with transcriptional complexes. We generated cell lines by retroviral over-expression of BCR-ABL1 in bone marrow cells from CDK6 knock-out mice. We then introduced HA-tagged variants of CDK6 - either wildtype CDK6 (CDK6_WT) or a C-terminally truncated variant of CDK6 lacking the last 32 amino acids of the protein (CDK6_delta-C). ChIP was performed with an antibody against the HA tag. CDK6 KO cell lines were used as controls.

2024-06-30 | E-MTAB-13798 | biostudies-arrayexpress

Gene expression profiling of murine BCR-ABL+ CDK6-wt and CDK6-KO cells

Project description:Dertermination of chromatin accessibility in murine BCR-ABL+ CDK6-wt and CDK6-KO cells

2020-11-24 | GSE156966 | GEO

Phosphochromatome profiling of C-terminally truncated CDK6

Project description:Pre/pro-B-cell lines were generated from bone marrow cells of Cdk6-/- mice by retroviral overexpression of the BCR-ABL (p185) fusion oncogene. These cell lines were transduced with constructs expressing HA-tagged versions of wildtype Cdk6 or of a C-terminally truncated variant of Cdk6 (HA-Cdk6-ΔC). Given the role of CDK6 in transcriptional regulation, we studied the phosphorylation of proteins associated with the chromatin (the phosphochromatome) using phospho-proteomics in cell lines that expressed C-terminally truncated CDK6, wildtype CDK6, or that had a CDK6 knock-out.

2024-12-19 | PXD059037 | Pride

Prolonged halting of gene expression in early G1 arrest by inhibition of CDK4/CDK6 reprograms myeloma cells for cytotoxic killing

Project description:By selective and reversible inhibition of CDK4/CDK6, we have developed a strategy to both inhibit proliferation and enhance cytotoxic killing of cancer cells. Induction of prolonged early-G1 arrest (pG1) by CDK4/CDK6 inhibition halts gene expression in early-G1 and prevents expression of genes programmed for other cell cycle phases. S-phase synchronization upon removal of the early-G1 block (pG1-S) fails to completely restore scheduled gene expression. Consequently, coordinate loss of IRF4 and gain of Bim and Noxa expression sensitize myeloma tumor cells to bortezomib-induced apoptosis in pG1 and more profoundly in pG1-S in vitro. Induction of pG1 and pG1-S by CDK4/CDK6 inhibition augments tumor-specific bortezomib killing in myeloma xenografts. Inhibition of CDK4/CDK6 in combination therapy thus represents a novel mechanism-based cancer therapy. PD 0332991 (PD) is the only known specific and reversible CDK4/CDK6 inhibitor. Gene expression was measured in myeloma MM1.S cells treated with PD (0.25 uM) in triplicate for 12, 24 or 36 h, or in cells released from G1, induced by 24hPD, for 4 or 18 h.

2012-04-06 | E-GEOD-35728 | biostudies-arrayexpress

Interactome of C-terminally truncated CDK6

Project description:Pre/pro-B-cell lines were generated from bone marrow cells of Cdk6-/- mice by retroviral overexpression of the BCR-ABL (p185) fusion oncogene. These cell lines were transduced with constructs expressing HA-tagged versions of wildtype Cdk6 or of a C-terminally truncated variant of Cdk6 (HA-Cdk6-ΔC). To study the interactome of HA-Cdk6-ΔC immunoprecipitation followed by mass spectrometry was performed.

2024-12-19 | PXD058474 | Pride

CDK6 antagonizes p53-induced responses during tumorigenesis

Project description:CDK6 induces a complex transcriptional program to block p53 in hematopoietic cells. CDK6 binds to the promoters of genes including p53-antagonists. Cells lacking CDK6 kinase function are required to mutate p53 to achieve a fully transformed immortalized state.

2018-08-06 | GSE113752 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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