Koraljka Husnjak

Koraljka Husnjak
Goethe-Universität Frankfurt am Main · Institute of Biochemistry

PhD

About

37
Publications
8,444
Reads
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2,799
Citations
Introduction
Koraljka Husnjak currently works at the Institute of Biochemistry, Goethe-Universität Frankfurt am Main. Koraljka does research in Cell Biology, Biochemistry and Chemical Biology with emphasis on post-translational modifications.
Additional affiliations
January 2010 - present
Goethe-Universität Frankfurt am Main
Position
  • Principal Investigator
April 2005 - December 2009
Goethe-Universität Frankfurt am Main
Position
  • PostDoc Position
May 2001 - March 2005
Ruđer Bošković Institute
Position
  • PhD Student

Publications

Publications (37)
Article
Full-text available
Caspase-2 represents an evolutionary conserved caspase, which plays a role in genotoxic stress-induced apoptosis, ageing-related metabolic changes, and in deleting aneuploid cells in tumors. Genetic deletion of caspase-2 leads to increased tumor susceptibility in vivo. The exact downstream signaling mechanism by which caspase-2 accomplishes its spe...
Preprint
Signalling through TNFR1 modulates proinflammatory gene transcription and programmed cell death, and its impairment causes autoimmune diseases and cancer. NEDD4-binding protein 1 (N4BP1) was recently identified as a critical suppressor of proinflammatory cytokine production ¹ , whose mode of action remained unknown. Here, we show that N4BP1 is a no...
Article
Full-text available
Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs mul-tiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed com-binatorial CRISPR libraries. We demonstrate that the library dis...
Preprint
Full-text available
Functional genomics studies in model organisms and human cell lines provided important insights into gene functions and their context-dependent role in genetic circuits. However, our functional understanding of many of these genes and how they combinatorically regulate key biological processes, remains limited. To enable the SpCas9-dependent mappin...
Article
Full-text available
Ubiquitination regulates nearly all cellular processes by coordinated activity of ubiquitin writers (E1, E2, and E3 enzymes), erasers (deubiquitinating enzymes) and readers (proteins that recognize ubiquitinated proteins by their ubiquitin-binding domains). By differentially modifying cellular proteome and by recognizing these ubiquitin modificatio...
Method
Full-text available
Simplicity, efficiency and versatility of the CRISPR/Cas system greatly contributed to its rapid use in a broad range of fields. Applications of unbiased CRISPR/Cas screenings are increasing and thus there is a growing need for unbiased and tailored CRISPR/Cas gRNA libraries. Conventional methods for gRNA library generation apply PCR and cloning te...
Article
Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidas...
Article
Ubiquitination is the most versatile posttranslational modification. The information is encoded by linkage type as well as chain length, which are translated by ubiquitin binding domains into specific signaling events. Chain topology determines the conformational space of a ubiquitin chain and adds an additional regulatory layer to this ubiquitin c...
Article
Ubiquitination controls a plethora of cellular processes. Modifications by linear polyubiquitin have so far been linked with acquired and innate immunity, lymphocyte development and genotoxic stress response. Until now, a single E3 ligase complex (LUBAC), one specific deubiquitinase (OTULIN) and a very few linear polyubiquitinated substrates have b...
Chapter
The covalent attachment of SUMO to lysine residues of cellular proteins serves as an important mechanism for the dynamic control of protein networks. SUMO conjugates typically mediate selected protein-protein interactions by binding to specific recognition modules. Identification of SUMO-binding proteins and the characterization of the binding moti...
Article
Full-text available
Rpn13 is an intrinsic proteasomal ubiquitin receptor that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results i...
Article
Full-text available
We recently identified the antioxidant protein Sestrin 2 (Sesn2) as a suppressor of platelet derived growth factor receptor beta (PDGFRβ) signaling and PDGFRβ signaling as an inducer of lung regeneration and injury repair. Here, we identified Sesn2 and the antioxidant gene inducer nuclear factor erythroid 2-related factor 2 (Nrf2) as positive regul...
Article
Full-text available
Mutations in the Park2 gene, encoding the RING-HECT hybrid E3 ubiquitin ligase parkin, are responsible for a common familial form of Parkinson's disease (PD). By mono- and polyubiquitinating target proteins, parkin regulates various cellular processes, including degradation of proteins within the 26S proteasome, a large multimeric degradation machi...
Article
Ubiquitin acts as a versatile cellular signal that controls a wide range of biological processes including protein degradation, DNA repair, endocytosis, autophagy, transcription, immunity, and inflammation. The specificity of ubiquitin signaling is achieved by alternative conjugation signals (monoubiquitin and ubiquitin chains) and interactions wit...
Article
In the past decade, the diversity of signals generated by the ubiquitin system has emerged as a dominant regulator of biological processes and propagation of information in the eukaryotic cell. A wealth of information has been gained about the crucial role of spatial and temporal regulation of ubiquitin species of different lengths and linkages in...
Article
Full-text available
Proteasomal receptors that recognize ubiquitin chains attached to substrates are key mediators of selective protein degradation in eukaryotes. Here we report the identification of a new ubiquitin receptor, Rpn13/ARM1, a known component of the proteasome. Rpn13 binds ubiquitin through a conserved amino-terminal region termed the pleckstrin-like rece...
Article
Full-text available
Targeted protein degradation is largely performed by the ubiquitin-proteasome pathway, in which substrate proteins are marked by covalently attached ubiquitin chains that mediate recognition by the proteasome. It is currently unclear how the proteasome recognizes its substrates, as the only established ubiquitin receptor intrinsic to the proteasome...
Article
Full-text available
Ubiquitin, best known as a degradation signal, is also a protein-sorting tag on endocytic cargoes and a regulatory switch on endocytic adaptor proteins. Parkin, a ubiquitin ligase whose mutations are associated with Parkinson's disease, has now been shown to control EGF-receptor internalization and Akt signalling by ubiquitination of the endocytic...
Article
Full-text available
The Pix/Cool proteins are involved in the regulation of cell morphology by binding to small Rho GTPases and kinases of the Pak family. Recently, it has been shown that betaPix/Cool-1 associates with the ubiquitin ligase Cbl, which appears to be a critical step in Cdc42-mediated inhibition of epidermal-growth-factor-receptor (EGFR) ubiquitylation an...
Article
The aims of this study were to assess the expression of protein products of c-myc, erbB-2, p53 and nm23-H1 gene in benign and malignant breast lesions, to estimate their possible coexpression and to correlate the results of immunohistochemical analysis with various clinicopathologic parameters. The method used was the immunohistochemical detection...
Article
Full-text available
CIN85 is a multidomain adaptor protein involved in Cbl-mediated down-regulation of epidermal growth factor (EGF) receptors. CIN85 src homology 3 domains specifically bind to a proline-arginine (PxxxPR) motif in Cbl, and this association seems to be important for EGF receptor endocytosis. Here, we report identification of novel CIN85 effectors, all...
Article
To determine the role of infections in miscarriages. Chorionic villi from aborted material were subjected to cytogenetic evaluation and analyzed for the presence of Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, human cytomegalovirus (HCMV), adeno-associated virus (AAV), and human papillomaviruses (HPV). Retrospective study. Uni...
Article
Full-text available
Two hundred eight cervical specimens from two groups of subjects, 165 nonpregnant women and 53 pregnant women with cervical intraepithelial neoplasia (CIN) of grades I to III, were positive by PCR analyses for human papillomaviruses (HPVs), adeno-associated virus type 2 (AAV 2), and human cytomegalovirus (HCMV) in 67, 6, and 4.1% of the cases, resp...
Article
Full-text available
CIN85 is a multidomain adaptor protein implicated in Cbl-mediated down-regulation of receptor tyrosine kinases. CIN85 binding to Cbl is increased after growth factor stimulation and is critical for targeting receptor tyrosine kinases to clathrin-mediated endocytosis. Here we report the identification of a novel polyproline-arginine motif (PXXXPR),...
Article
Cervical cancer is one of the most common malignancy both in incidence and in mortality in women worldwide. In Croatia, in 1993, cervical cancer took the third place following breast and stomach cancer. Therefore, early detection of HPV infection, as a leading cause of cervical cancer, is of major importance. In Croatian population, approximately 4...
Article
Full-text available
Expression of exogenous wild-type (wt) p53 protein can suppress the growth and/or induce apoptosis in different tumor cells. The effect of exogenous p21(WAF1/CIP1) expression is more controversial: while it can induce apoptosis in some cells, it can protect against p53-mediated apoptosis in others. We used adenoviral vectors to introduce p53 and p2...
Article
Causative agents of sexually transmitted diseases (STD) are different types of bacteria, viruses, fungi and protozoa. The last two decades of the twentieth century were marked with a sudden rise in the number of cases of STDs. Human immunodeficiency virus (HIV), which emerged in the 1980s, is the most prominent STD agent because of its fast spread...
Article
Full-text available
Infection with specific human papillomavirus (HPV) types is the strongest risk factor in cervical carcinogenesis. In this study we analysed, by means of polymerase chain reaction (PCR), cervical specimens obtained from consenting women with abnormal Pap smears collected from 1996 to 1998. Consensus- and type-specific-primers directed PCR were used...
Article
The polymerase chain reaction (PCR) methods enable the detection of large number of human papillomavirus (HPV) genotypes that infect the anogenital tract. In this study, two groups of cervical scrapes with abnormal cytomorphology were analysed. The first group was tested with three sets of consensus primers located within the L1 region of HPV genom...
Article
Full-text available
We investigated the distribution of genital human papillomaviruses (HPVs) among 171 consenting men of which four were involved twice in this study. The DNA was obtained from 7 normal tissues and 168 genital lesions of which 115 were diagnosed as condylomata acuminata, 17 as condylomata plana and 36 as HPV-associated lesions (papules, lichen-like le...
Article
Full-text available
The association between certain human papillomaviruses (HPV) and cervical intraepithelial neoplasia (CIN) is well documented, but still unknown among Croatian women. In 1995, women between the age of 17 and 64 with cytomorphologically abnormal smears (CIN I–IV) were tested for the presence of HPV. Consensus and specific primers were used in the pol...
Article
Full-text available
In an attempt to better understand the troubling issue of renal human papillomavirus (HPV) infection, fresh tumour specimens obtained by surgical extirpation from tumours were compared for the presence of HPV. All of the renal carcinoma samples were examined by PCR using two sets of consensus primers and the specific primer pairs for HPV 16, 18, an...

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Projects

Project (1)
Project
We are trying to determine interaction partners of dipeptidyl peptidase III (DPP III), cytosolic peptidase whose physiological role is still unknown. We are using yeast two-hybrid (Y2H) method to identify novel interacting partners of DPP III, and mass spectrometry interactome analysis to identify protein complexes DPP III takes part in. Putative interactors found by Y2H and MS approach will be analyzed by several low-throughput method. We aim to determine novel proteins that interact with DPP III and/or confirm interactions that are already published, as well as to confirm interactions obtained through Y2H by other, more specific methods, including GST and His pulldown, co-immunoprecipitation, FRET and ITC. We expect that by determining true interaction partners of DPP III, we might be able to decipher key physiological processes it is involved in.