A5037059775- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- DNA Repair Mechanisms
- Protein Tyrosine Phosphatases
- Renal and related cancers
- Protein Kinase Regulation and GTPase Signaling
- PI3K/AKT/mTOR signaling in cancer
- Mechanisms of cancer metastasis
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- RNA Research and Splicing
- Cell death mechanisms and regulation
- Pancreatic and Hepatic Oncology Research
- Cancer-related molecular mechanisms research
- Click Chemistry and Applications
- Microtubule and mitosis dynamics
- Renal cell carcinoma treatment
- Galectins and Cancer Biology
- Adenosine and Purinergic Signaling
- Histone Deacetylase Inhibitors Research
VIB-KU Leuven Center for Cancer Biology
2016-2025
KU Leuven
2013-2024
Dana-Farber Cancer Institute
2005-2023
Vlaams Instituut voor Biotechnologie
2023
VIB-KU Leuven Center for Microbiology
2020-2023
Sun Yat-sen University
2012
Harvard University
2005-2010
Broad Institute
2007-2010
Center for Human Genetics
2010
Brigham and Women's Hospital
2007-2010
Acting as a signal, hydrogen peroxide circumvents antioxidant defense by overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize peroxides. We show sestrins, family of proteins whose expression is modulated p53, are required for regeneration Prxs containing Cys-SO(2)H, thus reestablishing firewall. Sestrins contain predicted redox-active domain homologous to AhpD, enzyme catalyzing reduction bacterial Prx, AhpC. Purified Hi95 (sestrin 2) protein supports adenosine...
Regulation of RAS by ubiquitination The protein LZTR1 is mutated in human cancers and developmental diseases. Work from two groups now converges to implicate the regulating signaling small guanosine triphosphatase RAS. Steklov et al. showed that mice haploinsufficient for recapitulated aspects disease Noonan syndrome. Their biochemical studies associated with appears function as an adaptor promotes RAS, thus inhibiting its functions. Bigenzahn found a screen proteins whose absence led...
Abstract The simian virus 40 small t (SV40ST) oncoprotein interacts with protein phosphatase 2A (PP2A), an abundantly expressed family of serine–threonine phosphatases. This interaction is essential for the transformation human cells by SV40, and several PP2A subunits have been implicated as tumor suppressor genes. However, pathways controlled specific complexes involved in cell remain incompletely understood. Using a comprehensive loss-of-function approach, we identified 4 regulatory [B56α,...
Abstract Reversible phosphorylation plays a critical role in DNA repair. Here, we report the results of loss-of-function screen that identifies PP2A heterotrimeric serine/threonine phosphatases PPP2R2A, PPP2R2D, PPP2R5A, and PPP2R3C double-strand break (DSB) In particular, found PPP2R2A-containing complexes directly dephosphorylated ATM at S367, S1893, S1981 to regulate its retention DSB sites. Increased triggered by PPP2R2A attenuation dramatically upregulated activity downstream effector...
Abstract The p16INK4a protein is a principal cyclin-dependent kinase inhibitor that decelerates the cell cycle. Abnormally high levels of are commonly observed in human papillomavirus (HPV)–positive head and neck squamous carcinomas (HNSCC). We others found overexpression associated with improved therapy response survival patients HNSCC treated radiotherapy. However, functional role remains unexplored. Our results implicate regulation homologous recombination–mediated DNA damage...
Somatic missense mutations in the Ser/Thr protein phosphatase 2A (PP2A) Aα scaffold subunit gene PPP2R1A are among few genomic alterations that occur frequently serous endometrial carcinoma (EC) and carcinosarcoma, two clinically aggressive subtypes of uterine cancer with therapeutic options. Previous studies reported cancer-associated mutants exhibit defects binding to other PP2A subunits contribute development by a mechanism haploinsufficiency. Here we report on functional significance...
Research Article8 February 2016Open Access Source DataTransparent process OTUB1 triggers lung cancer development by inhibiting RAS monoubiquitination Maria Francesca Baietti Center for the Biology of Disease, VIB, Leuven, Belgium Human Genetics, KU Search more papers this author Michal Simicek Layka Abbasi Asbagh Enrico Radaelli Sam Lievens Department Medical Protein Research, Biochemistry, Gent University, Gent, Jonathan Crowther Mikhail Steklov Vasily N Aushev Institute Carcinogenesis,...
The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with PP2A scaffolding A subunit and alters activity by displacing regulatory B subunits from subunit. We have determined crystal structure full-length in complex at 3.1 Å resolution. consists an N-terminal J domain C-terminal unique contains two zinc-binding motifs. Both second motif interact intra-HEAT-repeat loops HEAT repeats 3–7 subunit, which overlaps...
Extracellular signal-regulated kinase (ERK)/mitogen-activated protein pathway activity is regulated by the antagonist function of activating kinases and inactivating phosphatases. Sustained ERK commonly observed in human malignancies; however, mechanisms which protected from phosphatase-mediated inactivation tumor tissue remain obscure. Here, we show that methylesterase PME-1-mediated inhibition phosphatase 2A promotes basal required for efficient growth factor response. Mechanistically,...
Dysregulated splicing is a common event in cancer even the absence of mutations core machinery. The aberrant long non-coding transcriptome constitutes an uncharacterized level regulation post-transcriptional events cancer. Here, we found that stress-induced RNA (lncRNA), LINC02657 or LASTR (lncRNA associated with SART3 splicing), upregulated hypoxic breast and essential for growth LASTR-positive triple-negative tumors. several types epithelial cancers due to activation JNK/c-JUN pathway....
The RAS pathway is among the most frequently activated signaling nodes in cancer. However, mechanisms that alter activity human pathologies are not entirely understood. prevalent post-translational modification within GTPase core domain of NRAS and KRAS ubiquitination at lysine 128 (K128), which significantly decreased cancer samples compared to normal tissue. Here, we found K128 creates an additional binding interface for GTPase-activating proteins (GAPs), NF1 RASA1, thus increasing GAP...
Abstract The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. share RAS/MAPK dysregulation and phenotypic manifestations numerous organ systems, causing lifelong at times life‐limiting medical complications. may benefit precision medicine approaches. For this reason, the Sixth International Symposium focused on exploring medicine. This meeting brought together basic science...
Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase pathways. In cancer cells, PP2A function can be compromised by several mechanisms, including sporadic mutations in its scaffolding A and regulatory B subunits or more frequently through overexpression of cellular inhibitors. Here, we identify a novel genetic mechanism which is recurrently affected human cancer, involving haploinsufficiency PPP2R4, gene encoding the activator PTPA. Notably, up to 70% patients showed...