A5088991911- Biotin and Related Studies
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- Advanced Proteomics Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Wnt/β-catenin signaling in development and cancer
- Cancer-related Molecular Pathways
- Parvovirus B19 Infection Studies
- Alzheimer's disease research and treatments
- COVID-19 Clinical Research Studies
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Cancer Cells and Metastasis
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Protein Tyrosine Phosphatases
University of Helsinki
2018-2025
Czech Academy of Sciences, Institute of Biotechnology
2021-2024
Helsinki Institute of Physics
2022-2023
University of Jyväskylä
2015-2016
University of Eastern Finland
2015
Abstract Protein-protein interactions govern almost all cellular functions. These complex networks of stable and transient associations can be mapped by affinity purification mass spectrometry (AP-MS) complementary proximity-based labeling methods such as BioID. To exploit the advantages both strategies, we here design optimize an integrated approach combining AP-MS BioID in a single construct, which term MAC-tag. We systematically apply MAC-tag to 18 subcellular 3 sub-organelle localization...
Abstract Transcription factors (TFs) interact with several other proteins in the process of transcriptional regulation. Here, we identify 6703 and 1536 protein–protein interactions for 109 different human TFs through proximity-dependent biotinylation (BioID) affinity purification mass spectrometry (AP-MS), respectively. The BioID analysis identifies more high-confidence interactions, highlighting transient dynamic nature many TF interactions. By performing clustering correlation analyses,...
Treatment options for COVID-19, caused by SARS-CoV-2, remain limited. Understanding viral pathogenesis at the molecular level is critical to develop effective therapy. Some recent studies have explored SARS-CoV-2-host interactomes and provided great resources understanding replication. However, host proteins that functionally associate with SARS-CoV-2 are localized in corresponding subnetwork within comprehensive human interactome. Therefore, constructing a downstream network including all...
Much cell-to-cell communication is facilitated by cell surface receptor tyrosine kinases (RTKs). These proteins phosphorylate their downstream cytoplasmic substrates in response to stimuli such as growth factors. Despite central roles, the functions of many RTKs are still poorly understood. To resolve lack systematic knowledge, we apply three complementary methods map molecular context and substrate profiles RTKs. We use affinity purification coupled mass spectrometry (AP-MS) characterize...
Short linear motifs (SLiMs) in disordered protein regions direct numerous protein-protein interactions, yet most remain uncharacterized. The Asn-Pro-Phe (NPF) motif is a well-known EH-domain ligand implicated endocytosis, but here we reveal that the non-catalytic subunit of human DNA polymerase ϵ(POLE2) also serves as general NPF-motif receptor. Using quantitative 'native holdup' assay, find POLE2 selectively binds diverse NPF-containing peptides, including canonical ligands (e.g., SYNJ1)...
Investigating repeated resistance training (RT) separated by a break enables exploration of the potential for proteomic memory RT-induced skeletal muscle growth, i.e. retained protein adaptations from previous RT. Our aim was to examine proteome response 10-week RT (RT1) followed cessation (i.e. detraining, DT), and finally, retraining (RT2). Thirty healthy, untrained participants conducted either periodic (RT1-DT-RT2, n = 17) or no-training control period (n 13) 20 weeks 11). included...
Autonomous parvoviruses encode at least two nonstructural proteins, NS1 and NS2. While is linked to important nuclear processes required for viral replication, much less known about the role of Specifically, function canine parvovirus (CPV) NS2 has remained undefined. Here we have used proximity-dependent biotin identification (BioID) screen proteins that associate with CPV Many these associations were seen both in noninfected infected cells, however, major type interacting shifted from...
The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset Alzheimer's disease (AD). ApoE interacts complement regulator factor H (FH), but role this interaction in AD pathogenesis unknown. Here we elucidate mechanism by which isoform-specific binding apoE to FH alters Aβ1-42-mediated neurotoxicity and clearance. Flow cytometry transcriptomic analysis reveal that reduce Aβ1-42 receptor 3 (CR3) subsequent phagocytosis microglia expression...
The paired-like homeobox transcription factor LEUTX is expressed in human preimplantation embryos between the 4- and 8-cell stages, then silenced somatic tissues. To characterize function of LEUTX, we performed a multiomic characterization using two proteomics methods three genome-wide sequencing approaches. Our results show that stably interacts with EP300 CBP histone acetyltransferases through its 9 amino acid transactivation domain (9aaTAD), as mutation this abolishes interactions....
Chromosomal translocations creating fusion genes are common cancer drivers. The oncogenic ETV6-NTRK3 (EN) gene joins the sterile alpha domain of ETV6 transcription factor with tyrosine kinase neurotrophin-3 receptor NTRK3. Four EN variants alternating break points have since been detected in a wide range human cancers. To provide molecular level insight into oncogenesis, we employed proximity labeling mass spectrometry approach to define context fusions. We identify total 237 high-confidence...
The continuous evolution of SARS-CoV-2 has led to the emergence several variants concern (VOCs) that significantly affect global health. This study aims investigate how these VOCs host cells at proteome level better understand mechanisms disease. To achieve this, we first analyzed (phospho)proteome changes infected with Alpha, Beta, Delta, and Omicron BA.1 BA.5 over time frames extending from 1 36 h post infection. Our results revealed distinct temporal patterns protein expression across...
The development of tissue fibrosis is complex and at the present time, not fully understood. Fibrosis, neurodegeneration cerebral angiomatosis (FINCA disease) have been described in patients with mutations NHL repeat-containing protein 2 (NHLRC2). However, molecular functions NHLRC2 are uncharacterized. Herein, we identified putative interacting partners for using proximity-labeling mass spectrometry. We also investigated function immortalized cells cultured from skin biopsies FINCA normal...
Abstract Wnt pathway dysregulation through genetic and non-genetic alterations occurs in multiple cancers, including ovarian cancer (OC). The aberrant expression of the non-canonical signaling receptor ROR1 is thought to contribute OC progression drug resistance. However, key molecular events mediated by that are involved tumorigenesis not fully understood. Here, we show enhanced neoadjuvant chemotherapy, Wnt5a binding can induce oncogenic via AKT/ERK/STAT3 activation cells. Proteomics...
Abstract Most patients with ovarian cancer (OC) are diagnosed at a late stage when there very few therapeutic options and poor prognosis. This is due to the lack of clearly defined underlying mechanisms or an oncogenic addiction that can be targeted pharmacologically, unlike other types cancer. Here, we identified protein tyrosine kinase 7 (PTK7) as potential new target in OC following multiomics approach using genetic pharmacological interventions. We performed proteomics analyses upon PTK7...
ABSTRACT The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation canine parvovirus during infection by confocal imaging in situ proximity ligation assay combined chromatin immunoprecipitation high-throughput sequencing. found that late infection, replication bodies were rich bearing modifications characteristic transcriptionally active chromatin, i.e., H3 lysine 27 (H3K27ac). H3K27ac, particular, was located close to...
Abstract ROR1, ROR2, and PTK7 are Wnt ligand-binding members of the receptor tyrosine kinase family. Despite their lack catalytic activity, these receptors regulate skeletal, cardiorespiratory, neurological development during embryonic fetal stages. However, overexpression in adult tissue is strongly connected to tumor metastasis, suggesting a strong pharmacological potential for molecules. Wnt5a ligand can activate receptors, but lead divergent signaling functional outcomes through...
Abstract Oncogenic gene fusions are estimated to account for up-to 20% of cancer morbidity. Recently sequence-level studies have established oncofusions throughout all tissue types. However, the functional implications identified often not been investigated. In this study, from a fusion detection approach (DEEPEST) were analyzed in detail. Of 28,863 oncofusions, we found almost 30% expected produce proteins with features both parent genes. Kinases and transcription factors main families...
Endometriosis is a common, chronic disease among fertile-aged women. Disease course may be highly invasive, requiring extensive surgery. The etiology of endometriosis remains elusive, though high level heritability well established. Several low-penetrance predisposing loci have been identified, but high-risk susceptibility undetermined. known to increase the risk epithelial ovarian cancers, especially endometrioid and clear cell types. Here, we analyzed Finnish family where four women...
Report14 August 2018Open Access Transparent process Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer Johanna Kondelin Medicum/Department Medical and Clinical Genetics, University Helsinki, Finland Genome-Scale Biology Research Program, Programs Unit, Search for more papers by this author Kari Salokas Institute Biotechnology, Helsinki Life Science, Lilli Saarinen Kristian Ovaska Heli Rauanheimo Roosa-Maria Plaketti Jiri Hamberg Xiaonan Liu...
Abstract The ErbB4 receptor isoforms JM-a and JM-b differ within their extracellular juxtamembrane (eJM) domains. Here, are used as a model to address the effect of structural variation in eJM domain tyrosine kinases (RTK) on downstream signaling. A specific JM-a-like sequence motif is discovered, its presence or absence (in JM-b-like RTKs) domains several RTKs demonstrated dictate selective STAT activation. STAT5a activation by including like shown involve interaction with oligosaccharides...
Chromosomal translocations creating fusion genes are common cancer drivers. The oncogenic ETV6-NTRK3 (EN) gene joins the sterile alpha domain of ETV6 transcription factor with thetyrosine kinase neurotrophin-3 receptor NTRK3. Four EN variants alternatingbreak points have since been detected in a wide range human cancers. To provide molecular levelinsight into oncogenesis, we employed proximity labeling mass spectrometry approach to definethe context fusions. We identify total 237...