Browse
Submit Data
Databases
API
Help

Dataset Information

211 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mouse CDC73 AP-MS in AML - PAF1 complex interactions with SETDB1 mediate promoter H3K9 methylation and transcriptional repression of Hoxa9 and Meis1 in acute myeloid leukemia

ABSTRACT: Here we performed AP-MS experiments to find novel binding partners of CDC73 in mouse M1 AML cells. We also utilized a CDC73 mutant that does not support AML cell growth to determine functional consequences of gainin/ losing protein-protein interactions on mutation of this protein.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Suspension Culture, Blood Cell, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: James Ropa

LAB HEAD: Andrew G Muntean

PROVIDER: PXD009439 | Pride | 2018-05-22

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

PAF1 complex interactions with SETDB1 mediate promoter H3K9 methylation and transcriptional repression of <i>Hoxa9</i> and <i>Meis1</i> in acute myeloid leukemia.

Ropa James J Saha Nirmalya N Chen Zhiling Z Serio Justin J Chen Wei W Mellacheruvu Dattatreya D Zhao Lili L Basrur Venkatesha V Nesvizhskii Alexey I AI Muntean Andrew G AG

Oncotarget 20180424 31

The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF ...[more]

PMID: 29774127

Similar Datasets

Affinify Purification of EZH2 and phosphodeficient EZH2 identifies phosphorylation dependent interactions of EZH2

Project description:Overexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. EZH2 has been mainly studied as the catalytic component of the Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how EZH2 drives metastasis despite the low H3K27me3 levels observed in ER- breast cancer is unknown. We have shown that in human invasive carcinomas and distant metastases, cytoplasmic EZH2 phosphorylated at T367 is significantly associated with ER- disease and low H3K27me3 levels. Here, we explore the interactome of EZH2 and of a phosphodeficient mutant EZH2_T367A. We identified novel interactors of EZH2, and identified interactions that are dependent on the phosphorylation and cellular localization of EZH2 that may play a role in EZH2 dependent metastatic progression.

2018-07-03 | PXD010073 | Pride

FLAG-PHF3 interactome in HEK293 cells

Project description:FLAG-hPHF3 was transiently expressed in human HEK293 cells, followed by anti-FLAG immunoprecipitation, on-bead digest and NanoLC-MS analysis.

2022-02-17 | PXD026292 | Pride

HTT-OMNI: A Web-based Platform for Huntingtin Interaction Exploration and Multi-omics Data Integration

Project description:We have developed a web-based platform for HTT PPI visualization, exploration, and multi-omic integration called HTT-OMNI. We demonstrate the utility of this platform not only for exploring and filtering existing huntingtin (HTT) PPIs, but also for investigating user-generated omics datasets. For example, we demonstrate the comparison of a published HTT IP-MS experiment, performed in the striatum brain region of a mouse HD model, to unpublished HTT IP-MS experiments in the cortex brain region. Overall, HTT-OMNI summarizes and integrates known HTT PPIs with polyQ-dependent transcriptome and proteome measurements, providing an all-in-one exploratory platform that facilitates the prioritization of target genes that may contribute to HD pathogenesis.

2022-08-15 | PXD034158 | Pride

RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA

Project description:Alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR) mechanism of telomere elongation that controls proliferation in subsets of highly aggressive cancer. Recent studies have revealed that TERRA (telomere repeat-containing RNA) acts to initiate ALT-associated HDR (ALT-HDR). Here we report that RAD51AP1, a crucial ALT factor, interacts with TERRA and utilizes it to generate D- and R- loop HR intermediates. We also show that RAD51AP1 binds to and may generate and potentially stabilize TERRA-containing R-loops as RAD51AP1 depletion reduces R-loop formation at telomere DNA breaks. Proteomic analyses uncover a new role for RAD51AP1 mediated TERRA R-loop homeostasis in a mechanism of chromatin-directed suppression of TERRA and prevention of transcription-replication collisions during ALT-HDR. Intriguingly, we find that both TERRA binding and this non-canonical function of RAD51AP1 require its intrinsic SUMO-SIM regulatory axis. These findings provide new insights into the multi-contextual functions of RAD51AP1 within the ALT mechanism and regulation of TERRA.

2024-01-26 | PXD035943 | Pride

Proteomic analysis uncover a new function and mode of action for mDia2

Project description:mDia2 is an auto-inhibited Formin influencing actin dynamics upon conversion to the active conformation. mDia2 regulates actin-based protrusions and cell invasion, cell differentiation, vesicle trafficking and cytokinesis. However, whether mDia2 has additional functions and how its action is functionally specified remain unknown. Here we draw the interactome of auto-inhibited and constitutively active mDia2 to address these issues. We embed mDia2 in protein networks accounting for its attributed functions and unexpectedly link it to the Ubiquitin Proteasome System. Taking FBXO3 as a test case, we show that mDia2 binds FBXO3 and p53, and regulates p53 transcriptional activity in an actin-nucleation-independent and conformation-insensitive manner. Increased mDia2 and FBXO3 levels elevate p53 activity and expression thereby sensitizing cells to p53-dependent apoptosis, whereas their decrease produces opposite effects. Thus, we discover a new role of mDia2 in p53 regulation suggesting that the closed conformation is biologically active and an FBXO3-based mechanism to functionally specify mDia2’s activity.

2015-01-06 | PXD000175 | Pride

Huntingtin polyglutamine expansion modulates protein interaction dynamics in the striatum

Project description:Huntington’s disease is a monogenic disorder, with only one known causative gene, huntingtin (HTT). Expansion of a trinucleotide (CAG) repeat within the HTT gene results in a mutant protein containing polyglutamine (polyQ) stretches. While mutant HTT is the primary driver of cellular degeneration in the brain, the molecular and cellular mechanisms are incompletely understood. To further understand the role of polyQ in disease pathogenesis, we studied the dynamics of HTT protein-protein interactions (PPIs) in the striatum of mice with wild-type (Q20) and mutant (Q140) HTT at pre-symptomatic and manifest HD ages using label-free and isotope-labeled IP-MS approaches. Combining these approaches, we demonstrated that HTT PPI dynamics are distinct in early and later disease phases. Computational analysis pointed to early protein interaction changes involving synaptic transmission and vesicle fusion functions, while later interactions underlie changes in synapse morphogenesis and impact the actin cytoskeletal network.

2022-02-20 | PXD025510 | Pride

HRD1 IP-MS in WT and SEL1L deficiency HEK293T cells

Project description:To gain further insights into the role and importance of SEL1L in HRD1 ERAD, we performed unbiased proteomics LC-MS analyses to map SEL1L and HRD1 interactomes in WT and SEL1L-/-, WT and HRD1-/- HEK293T cells, respectively.

2024-01-10 | PXD043674 | Pride

Interactome analysis of PYHIN immune regulators

Project description:The human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are regulators of immune response, transcription, apoptosis, and cell cycle. However, their protein interactions and underlying mechanisms remain largely uncharacterized. Here, we provide the interaction network for all PYHIN proteins. By designing a cell-based inducible system and integrating microscopy, immunoaffinity capture, quantitative mass spectrometry, and bioinformatics, we identified over 300 PYHIN interactions reflective of diverse functions.

2015-03-12 | PXD001572 | Pride

Interactome of alanine:glyoxylate aminotransferase polimorphic forms

Project description:This dataset includes raw data on the interactome of two polymorphic forms of alanine:glyoxylate aminotransferase (AGT), the major allele, AGT-Ma and the minor one AGT-Mi. Theproteins were expressed in HEK293 cells and the interactome was analysed using co-immunoprecipitation mass spectrometry (IP-MS)

2022-05-04 | PXD025661 | Pride

TFIIIC dinamically binds Alu elements to control gene expression through chromatin looping

Project description:Folding of the mammalian genome is governed by architectural proteins, such asCTCF. TFIIIC, a RNA polymerase III transcription factor, has been identified as aninsulator but its role in genome topology is totally unknown. Here, we show that TFIIICestablishes long-range genomic interactions that affect gene expression. Upon serumstarvation (SS), TFIIIC occupancy increases at Alu elements (AEs) near promoters ofcell cycle-related genes. Bound AEs become H3K18 hyper-acetylated and fold tocontact distal pre-loaded CTCF sites near other cell cycle genes. The promoters ofthese genes also become hyper-acetylated ensuring their basal transcription during SSand their increased expression during serum re-exposure. Ablation of TFIIIC ordeletion of the TFIIIC-bound AE that loops to the G2/M cycling F (CCNF) locus affectsits expression and nuclear positioning. These results illustrate a novel function ofhuman TFIIIC in changing 3D genome topology through the epigenetic state of AEs.

2020-05-26 | PXD011250 | 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