Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CIP2A-TOPBP1 Interaction in Human Mitotic Cells

ABSTRACT: We investigate the implications of DNA double strand breaks in the human genome, regarding the progression and treatment of various cancer types. During mitosis, the canonical DNA repair mechanisms are suspended while broken chromosomes get temporarily stabilized through so-called adapter proteins. We already knew that TOPBP1 is involved in that process and recently, we identified another Protein which recruits TOPBP1 to sites of damage. After mapping the interaction site on TOPBP1 we attempted to pull down CIP2A using a fragment of the binding domain, followed by chromatography-tandem-mass spectrometry analysis, the results of which we share in this upload.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Alain Jeanrenaud

LAB HEAD: Manuel Guido Stucki

PROVIDER: PXD034100 | Pride | 2022-07-19

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Ovarian cancers with low CIP2A tumor expression constitute an APR-246 sensitive disease subtype

Project description:Identification of ovarian cancer (OvCa) patient subpopulations with increased sensitivity to targeted therapies could offer significant clinical benefit. We report that 22 % of the high grade OvCa tumors at diagnosis express CIP2A oncoprotein at low levels. Further, regardless of their significantly lower likelihood of disease relapse after standard chemotherapy, a portion of relapsed tumors retain their CIP2A-deficient phenotype. Through a screen for therapeutics that would preferentially kill CIP2A-deficient OvCa cells, we identified reactive oxygen species inducer APR-246, tested previously in OvCa clinical trials. Consistent with CIP2A-deficient OvCa subtype in humans, CIP2A is dispensable for development of MISIIR-Tag-driven mouse OvCa tumors. Nevertheless, CIP2A null OvCa tumor cells from MISIIR-Tag mice displayed APR-246 hypersensitivity both in vitro and in vivo. Mechanistically, the lack of CIP2A expression hypersensitizes the OvCa cells to APR-246 by inhibition of NF-kB activity. Accordingly, combination of APR-246 and NF-kB inhibitor compounds strongly synergized in killing of CIP2A positive OvCa cells. Collectively, the results warrant consideration of clinical testing of APR-246 for CIP2A-deficient OvCa tumor subtype patients. Results also reveal CIP2A as a candidate APR-246 combination therapy target for ovarian cancer.

2022-02-02 | GSE195984 | GEO

TopBP1 associated with RNA in HEK293T cells

Project description:We report the TopBP1 associated with RNA via using sequencing of RNA isolated by PAR-CLIP.

2022-09-23 | GSE213073 | GEO

RNA sequencing of control and CIP2A siRNA silenced basal-like breast cancer cell line HCC38

Project description:The purpose is to study the transcriptional changes in basal like breast cancer cell line HCC38 on depletion of CIP2A. We have used 3 unique siRNA sequences of CIP2A and 3 control samples (Mock and 2 unique non-targeting sequences) for the RNA Seq. We identified differentially expressed genes in CIP2A knockdown conditions compared to the control samples and identified pathways regulated by CIP2A in this cell line using GSEA.

2021-04-27 | GSE173302 | GEO

TOPBP1 Shapes XY Silencing Dynamics during Meiosis to Ensure Male Fertility

Project description:TOPBP1 and other DNA damage response proteins play an important role in meiotic sex chromosome inactivation. We investigate a mutant mouse with a mutation in the BRCT5 domain of TOPBP1 and use single-cell RNA-seq to investigate the effect of the mutation on XY silencing.

2024-02-09 | GSE232588 | GEO

RNA-sequencing of control and DMBA-treated WT and Cip2a-/- mouse mammary glands

Project description:The purpose is to study DMBA-induced transcriptome in WT and in Cip2a-/- mouse mammary gland tissues. We identified differentially expressed genes in DMBA-induced mammary gland in WT vs. Cip2a-/- mouse mammary glands.

2021-04-28 | GSE173405 | GEO

Cancerous inhibitor of PP2A (CIP2A) Constrains Th17 Differentiation by Modulating STAT3 Signaling

Project description:Genome-wide RNA seq data profile gene expression in human CIP2A silenced Th17 cells

2019-08-13 | GSE118094 | GEO

Downstream Target Screening of TopBP1 in differentiated HPV-positive keratinocytes

Project description:TopBP1 is more than a DNA damage factor. The knockdown indicates it could have transcriptional regulatory function and we validated this by examining E2F1/p73 pathway.

2018-11-01 | GSE122018 | GEO

cAMP/PKA signaling promotes AKT deactivation via reducing CIP2A expression, thereby facilitating decidualization

Project description:Decidualization is a progesterone-initiated differentiation concerning the endometrium and is dedicated to supporting the placenta and embryo development. During the process, cAMP signaling is widely known to be indispensable, but the details are not fully understood. In this study, we show that cAMP signaling promotes AKT deactivation in endometrial stromal cells, which favors their decidualization. The deactivation of AKT is found to be a consequence of the reduced expression of several inhibitors of PP2A, the major phosphatase of AKT, with CIP2A being the most prominent. To show that CIP2A loss is obligatory for decidualization, we performed this ATAC-seq analysis. Persistent CIP2A expression impairs the chromatin accesibility remodeling during decidualization.

2023-02-06 | GSE224212 | GEO

CIP2A negatively regulates Th17 differentiation

Project description:Interleukin 17 (IL-17) producing T helper 17 (Th17) cells are critical drivers of pathogenesis in a variety of autoimmune and inflammatory diseases. Strategies to mitigate excessive Th17 response thus remain an attractive target for immunotherapies. Here we report that Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) regulates IL-17 production by Th17 cells in human and mouse. Using CIP2A knock-out (KO) mice and siRNA-mediated CIP2A silencing in human primary CD4+ T cells, we demonstrated that CIP2A silencing results in a significant increase in IL-17 production. Interestingly, CIP2A deficient Th17 cells were characterized by increased strength and duration of STAT3 (Y705) phosphorylation. Genome-wide gene expression profile as well as the p-STAT3 (Y705) interactome of CIP2A deficient Th17 cells identified that CIP2A regulates the strength of the interaction between Acylglycerol kinase (AGK) and STAT3, and thereby, modulates STAT3 phosphorylation as well as expression of IL-17 in Th17 cells. Our results uncover the physiological function of CIP2A in Th17 cells and provides new opportunities for therapeutic intervention in Th17 cell mediated diseases.

2020-05-26 | PXD010612 | Pride

CIP2A interactome in human Th17 Cells

Project description:CIP2A immunoprecipitation (IP) was carried out with two specific anti CIP2A antibodies that recognize distinct regions of CIP2A protein and respective Immunoglobulin G (IgG) were used in control IPs as a negative control. The digested samples were analyzed by LC-MS/MS to identify CIP2A protein network.

2021-09-08 | PXD008983 | Pride

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