Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA254155 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1504832.fastq.gz | Fastqsanger.gz | |||
| SRR1504833.fastq.gz | Fastqsanger.gz | |||
| SRR1504834.fastq.gz | Fastqsanger.gz | |||
| SRR1504835.fastq.gz | Fastqsanger.gz |
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Project description:The catalytic activity of Abl family kinases is tightly regulated in cells by a complex set of intra- and intermolecular interactions and post-translational modifications. Abl family kinases are activated by diverse cellular stimuli, one of them being receptor tyrosine kinase signaling. For example, platelet-derived growth factor receptor beta (PDGFRβ) has been identified as a potent activator of Abl family kinases. However, the molecular mechanism by which PDGFRβ engages and activates Abl family kinases is not known. We report here the molecular mechanism by which PDGFRβ interacts, phosphorylates and activates Abl2 kinase. We found that PDGFRβ binds and phosphorylates Abl2 both in vitro and in cells. We also identified several novel PDGFRβ phosphorylation sites on Abl2, including Y116, Y139 and Y161 on the SH3 domain, and Y299, Y303 and Y310 on the kinase domain. Of notable interest, Y116, Y161, Y272 and Y310 are all located near the SH3/SH2-kinase linker interface, which help maintain Abl family kinases in an auto-inhibited conformation. Mutation of these four tyrosine (Y116, Y161, Y272 and Y310) to phenylalanine abrogated PDGFRβ-mediated activation of Abl2 kinase activity. These findings provide a mechanism to understand how receptor tyrosine kinases activate Abl family kinases, and how Abl kinases are precisely regulated through different phosphorylation events.
2022-02-17 | PXD025896 | Pride
Project description:DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and attenuating aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domains. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1 Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathologically and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA processing-independent role for DGCR8 in maintaining heterochromatin organization and attenuating senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders.
2019-05-28 | PXD013856 | Pride
Project description:Tyrosine kinase c-Abl couples RNA polymerase II transcription to an RNA-dependent DNA damage response
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Project description:Critical DNA repair pathways become deranged during cancer development. This vulnerability may be exploited with DNA-targeting chemotherapy. Topoisomerase II inhibitors induce double-strand breaks which are detrimental to the cell, if not repaired. This repair process requires high-fidelity functional homologous recombination or error-prone non-homologous recombination. If either of these pathways is targeted, the compensatory pathway may rescue the cells and induce treatment resistance. c-Abl is a protein tyrosine kinase that is involved in cell differentiation, cell division, cell adhesion, and stress response including DNA damage induced stress. Here we used a low dose topoisomerase II inhibitor mitoxantrone to induce DNA damage and c-Abl kinase inhibitor imatinib in combination and studied the drug effects at transcriptomic level. The microarray data suggests that DNA repair, particularly homologous recombination, is downregulated together with alterations in cell cycle regulation. The data prompted to further validation assays on functional level which are shown in the original publication.
2021-09-22 | E-MTAB-9475 | biostudies-arrayexpress
Project description:miR-seq to find miRs that are induced by DNA damage and whose induction requires ABL kinase activity Use p53-inactive HEK293T cells. Use doxorubicin to induce DNA damage. Use imatinib co-treatment to inhibit ABL kinase activity
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Project description:Anaysis of mRNA changes in HeLa cells following knockdown of Drosha or DGCR8. Drosha is a nuclear RNase III that carries out microRNA (miRNA) processing by cleaving primary microRNA transcript (pri-miRNA). DGCR8 is an essential co-factor of Drosha. Keywords: gene expression array-based (RNA / in situ oligonucleotide)
2009-02-05 | GSE13639 | GEO
Project description:Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) can be subdivided into different categories based on genetic abnormalities. One type of pre-B ALL is characterized by the presence of the Philadelphia (Ph) chromosome, the derivative chromosome 22 that is one product of a reciprocal translocation between chromosomes 22 and 9. The 22/9 translocation fuses the 5’ part of the BCR gene to the 3’ end of the c-ABL gene. The resulting BCR/ABL fusion encodes a Bcr/Abl protein with deregulated Abl kinase activity. Two major fusion proteins are found in Ph-positive leukemias which differ in molecular weight and the size of the Bcr moiety. The P190 Bcr/Abl protein is common in Ph-positive ALL. Targeted tyrosine kinase inhibitors such as nilotinib are used therapeutically to treat this type of leukemia. The 22/9 translocation fuses the 5’ part of the BCR gene to the 3’ end of the c-ABL gene. The resulting BCR/ABL fusion encodes a Bcr/Abl protein with deregulated Abl kinase activity. Two major fusion proteins are found in Ph-positive leukemias which differ in molecular weight and the size of the Bcr moiety. The P190 Bcr/Abl protein is common in Ph-positive ALL. Targeted tyrosine kinase inhibitors such as nilotinib are used therapeutically to treat this type of leukemia.
2018-02-05 | GSE110104 | GEO
Project description:Gene expression profile variation between 4 BCR-Abl transduced cell lines: <br> 1-Mouse DA1-3b cell line as reference, <br> 2-DR1 imatinib resistant clone with E255K BCR-abl mutation<br> 3-DRBMSR 2 dasatinib resistant clone with E255K and T315I BCR-Abl mutation.<br> 4-DRBMSR 7 dasatinib resistant clone with E255K and T315I and V299L BCR-Abl mutation<br> <br> BCR-ABL is an oncogenic tyrosine kinase involved in the development of chronic myelogenous leukaemia (CML).
2007-08-01 | E-MEXP-772 | biostudies-arrayexpress
Project description:Anaysis of mRNA changes in HeLa cells following knockdown of Drosha or DGCR8. Drosha is a nuclear RNase III that carries out microRNA (miRNA) processing by cleaving primary microRNA transcript (pri-miRNA). DGCR8 is an essential co-factor of Drosha. Experiment Overall Design: siRNA against Drosha or DGCR8 were trasnfected into HeLa cells. siRNA against GFP was used as a control. Biologically duplicated total RNAs were prepared from HeLa cells, 24 hrs and 48 hrs after siRNA transfection.
2009-02-21 | E-GEOD-13639 | biostudies-arrayexpress
Project description:Comparative analysis of BCR-ABL tyrosine kinase inhibitors in BCR-ABL positive K562 cells
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