Mariola Zaleska

Mariola Zaleska
Institute of Cancer Research · Division of Structural Biology

PhD in Cardiovascular Medicine

About

14
Publications
696
Reads
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48
Citations
Additional affiliations
July 2017 - present
Institute of Cancer Research
Position
  • Research Officer
July 2015 - June 2017
University of Cambridge
Position
  • Research Associate
July 2014 - June 2015
King's College London
Position
  • Research Associate
Education
January 2009 - January 2010
University of Huddersfield
Field of study
  • Analytical Bioscience
October 2007 - June 2008
University of Huddersfield
Field of study
  • Molecular and Cellular Biology
October 2004 - October 2007
University of Silesia in Katowice
Field of study
  • Biotechnology of Plants and Microorganisms

Publications

Publications (14)
Article
Full-text available
The Wnt/β-catenin pathway is a highly conserved, frequently mutated developmental and cancer pathway. Its output is defined mainly by β-catenin’s phosphorylation- and ubiquitylation-dependent proteasomal degradation, initiated by the multi-protein β-catenin destruction complex. The precise mechanisms underlying destruction complex function have rem...
Article
Full-text available
The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in cancer-relevant processes, including Wnt/β-catenin signalling, Hippo signalling and telomere maintenance. The ARCs recognise a c...
Article
Full-text available
Tankyrases are poly(ADP-ribose)polymerases (PARPs) which recognize their substrates via their ankyrin repeat cluster (ARC) domains. The human tankyrases (TNKS/TNKS2) contain five ARCs in their extensive N-terminal region; of these, four bind peptides present within tankyrase interactors and substrates. These short, linear segments, known as tankyra...
Preprint
Full-text available
The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in cancer-relevant processes, including Wnt/beta-catenin signaling and telomere maintenance. The ARCs recognise a conserved tankyra...
Article
Double mutation of Q41L and K75I in the N-domain of calmodulin (N-Cam) stabilizes the closed form of N-Cam such that binding of Ca2 + in solution no longer triggers a conformational change to the open form, and its Ca2 + binding affinity decreases dramatically. To further investigate the solvation effects on the structure, Ca2 + binding affinity an...
Article
Full-text available
Ms1 (also known as STARS and ABRA) has been shown to act as an early stress response gene in processes as different as hypertrophy in skeletal and cardiac muscle and growth of collateral blood vessels. It is important for cardiac development in zebrafish and is upregulated in mouse models for cardiac hypertrophy as well as in human failing hearts....
Data
Top 50 hits of DALI search of the PDB with the structure of ABD2. Proteins that are not involved in DNA binding are marked with a blue star. Structures used in the superposition in Fig 1D are marked with red stars. (PDF)
Data
Western blot validation of new antibody against Ms1. The antibody (aABD2chn) was generated for detection of endogenous Ms1. It was validated by western blots with myc-tagged full length Ms1 expressed in COS cells (left); western blots of endogenous Ms1 in muscle tissue extracts with untreated and blocked antibody (lower left); western blots of over...
Data
Effects of potential interactions of the N-terminal extension of ABD2 on stability and NMR spectra of ABD2. A significant increase in stability of > 7°C is seen for the addition of 23 amino acids at the N-terminus of ABD2.This addition leads to considerable chemical shift changes around helix one to which it would need to pack to allow the AT-hook...
Data
Backbone dynamics analysis of ABD2. On the left are shown the experimental values for 15N T1, T2 and heteronuclear NOE recorded at 500 MHz. On the right are two parameters from the Lipari-Szabo analysis, the order parameter S2 and the exchange contribution Rex. Apart from a small region in the wing there is little flexibility in the compact structu...
Data
Alignment of a selection of full length Ms1 protein sequences. A selection of functional features, structural domains and secondary structure elements are shown by bars. Experimentally identified phosphorylation sites that are conserved amongst mammals are indicated by red stars. (PDF)
Data
Immunofluorescence validation of new antibody Ms1. Immunofluorescence detection of transfected full length myc-tagged Ms1 in HeLa cells using anti-myc as well as aABD2chn antibodies (left) and immunofluorescence detection of endogenous Ms1 in NRCs with untreated and blocked aABD2chn (right). (PDF)
Article
MS1 is a protein predominantly expressed in cardiac and skeletal muscle that is upregulated in response to stress and contributes to development of hypertrophy. In the aortic banding model of left ventricular hypertrophy, its cardiac expression was significantly upregulated within 1 h. Its function is postulated to depend on its F-actin binding abi...

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Projects

Project (1)
Project
In electrically-excitable cells, the voltage-gated sodium (Nav) channel initiates the action potential. Sodium channels are major pharmacological targets and are implicated in pathologies such as heart disease, epilepsy, and chronic pain. The sodium channel consists of a ~ 260 kDa alpha-subunit with associated ~ 35-40 kDa beta-subunits. The beta-subunits modulate channel electrophysiological behaviour and help traffic the channel to the plasma membrane. There are ten alpha-subunit and four beta-subunit genes, expressed in distinct tissue-specific patterns. All Nav beta-subunits possess a single extracellular immunoglobulin (Ig) domain, connected via a stalk to an alpha-helical transmembrane domain and an intracellular carboxy-terminal region. We are studying the role played by the beta 3-subunit in Nav channel structure and function. In mice, deletion of the beta 3-subunit gene (Scn3b) is associated with cardiac arrhythmias. To provide a better understanding of the beta 3-subunit, we investigated its structure using X-ray crystallography. We have shown that the beta3-subunits can trimerise via their Ig domains, and induce the formation of Nav channel alpha-subunit oligomers, including trimers. These results provide a new interpretation of previous electrophysiological data, and raise a new set of questions. Does the cross-linking of Nav channels by beta 3 lead to functionally coupled channels? Can different Nav alpha-subunits be cross-linked together? Do the beta-subunits help stabilise the Nav channel into larger-scale protein clusters on the plasma membrane? Selected publications: Namadurai, S., Yereddi, N.R., Cusdin, F.S., Huang, C-L., Chirgadze, D.Y., and Jackson, A.P. (2015) A new look at sodium channel β subunits. Open Biol pii: 140192. Namadurai, S., Balasuriya, D., Rajappa, R., Wiemhofer, M., Stott, K., Klingauf, J., Edwardson, J. M., Chirgadze, D. Y., and Jackson, A. P. (2014) Crystal Structure and Molecular Imaging of the Nav Channel beta3 Subunit Indicates a Trimeric Assembly. J Biol Chem 289, 10797-10811 Yereddi, N. R., Cusdin, F. S., Namadurai, S., Packman, L. C., Monie, T. P., Slavny, P., Clare, J. J., Powell, A. J., and Jackson, A. P. (2013) The immunoglobulin domain of the sodium channel beta3 subunit contains a surface-localized disulfide bond that is required for homophilic binding. FASEB J 27, 568-580 Cusdin, F. S., Nietlispach, D., Maman, J., Dale, T. J., Powell, A. J., Clare, J. J., and Jackson, A. P. (2010) The sodium channel beta3-subunit induces multiphasic gating in NaV1.3 and affects fast inactivation via distinct intracellular regions. J Biol Chem 285, 33404-33412 Merrick, E. C., Kalmar, C. L., Snyder, S. L., Cusdin, F. S., Yu, E. J., Sando, J. J., Isakson, B. E., Jackson, A. P., and Patel, M. K. (2010) The importance of serine 161 in the sodium channel beta3 subunit for modulation of Na(V)1.2 gating. Pflugers Arch 460, 743-753 Hakim, P., Brice, N., Thresher, R., Lawrence, J., Zhang, Y., Jackson, A. P., Grace, A. A., and Huang, C. L. (2010) Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties. Acta Physiol (Oxf) 198, 47-59