ORCID Profile
0000-0002-9357-1480
Current Organisations
University of Jyväskylä
,
ETH Zurich
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Publisher: Springer Science and Business Media LLC
Date: 28-02-2023
DOI: 10.1038/S41467-023-36693-9
Abstract: The protein phosphatase 2A (PP2A) heterotrimer PP2A-B56α is a human tumour suppressor. However, the molecular mechanisms inhibiting PP2A-B56α in cancer are poorly understood. Here, we report molecular level details and structural mechanisms of PP2A-B56α inhibition by an oncoprotein CIP2A. Upon direct binding to PP2A-B56α trimer, CIP2A displaces the PP2A-A subunit and thereby hijacks both the B56α, and the catalytic PP2Ac subunit to form a CIP2A-B56α-PP2Ac pseudotrimer. Further, CIP2A competes with B56α substrate binding by blocking the LxxIxE-motif substrate binding pocket on B56α. Relevant to oncogenic activity of CIP2A across human cancers, the N-terminal head domain-mediated interaction with B56α stabilizes CIP2A protein. Functionally, CRISPR/Cas9-mediated single amino acid mutagenesis of the head domain blunted MYC expression and MEK phosphorylation, and abrogated triple-negative breast cancer in vivo tumour growth. Collectively, we discover a unique multi-step hijack and mute protein complex regulation mechanism resulting in tumour suppressor PP2A-B56α inhibition. Further, the results unfold a structural determinant for the oncogenic activity of CIP2A, potentially facilitating therapeutic modulation of CIP2A in cancer and other diseases.
Publisher: Wiley
Date: 29-05-2014
DOI: 10.1002/JBM.A.35234
Abstract: Poly(vinylidene fluoride) (PVDF) is a biocompatible material with excellent electroactive properties. Nonelectroactive α-PVDF and electroactive β-PVDF were used to investigate the substrate polarization and polarity influence on the focal adhesion (FA) size and number as well as on human adipose stem cells (hASCs) differentiation. hASCs were cultured on different PVDF surfaces adsorbed with fibronectin and FA size and number, total adhesion area, cell size, cell aspect ratio and FA density were estimated using cells expressing vinculin fused to enhanced green fluorescent protein. Osteogenic differentiation was also determined using a quantitative alkaline phosphatase assay. The surface charge of the poled PVDF films (positive or negative) influenced the hydrophobicity of the s les, leading to variations in the conformation of adsorbed extracellular matrix proteins, which ultimately modulated the stem cell adhesion on the films and induced their osteogenic differentiation.
Publisher: American Chemical Society (ACS)
Date: 07-09-2016
Abstract: Development of a label-free ultrasensitive nanosensor for detection of bacteria is presented. Sensitive assay for Gram-positive bacteria was achieved via electrostatic attraction-guided plasmonic bifacial superstructure/bacteria/columnar array assembled in one step. Dynamic optical hotspots were formed in the hybridized nanoassembly under wet-dry critical state lifying efficiently the weak vibrational modes of three representative food-borne Gram-positive bacteria, that is, Staphylococcus xylosus, Listeria monocytogenes, and Enterococcus faecium. These three bacteria with highly analogous Raman spectra can be effectively differentiated through droplet wet-dry critical SERS approach combined with 3D PCA statistical analysis so that highly sensitive discrimination of bacterial species and s les containing mixtures of bacteria can be achieved.
Publisher: Wiley
Date: 11-11-2014
DOI: 10.1002/JBM.A.35368
Abstract: This work reports on the influence of the substrate polarization of electroactive β-poly(vinylidene fluoride) (β-PVDF) on human adipose stem cells (hASCs) differentiation under static and dynamic conditions. hASCs were cultured on different β-PVDF surfaces (non-poled and "poled -") adsorbed with fibronectin and osteogenic differentiation was determined using a quantitative alkaline phosphatase assay. "Poled -" β-PVDF s les promote higher osteogenic differentiation, which is even higher under dynamic conditions. It is thus demonstrated that electroactive membranes can provide the necessary electromechanical stimuli for the differentiation of specific cells and therefore will support the design of suitable tissue engineering strategies, such as bone tissue engineering.
Publisher: Elsevier BV
Date: 02-2017
Publisher: American Chemical Society (ACS)
Date: 28-05-2015
Publisher: American Chemical Society (ACS)
Date: 04-02-2015
DOI: 10.1021/LA503213F
Abstract: We describe the development of a reference biosensor surface, based upon a binary mixture of oligo-ethylene glycol thiols, one of which has biotin at the terminus, adsorbed onto gold as self-assembled monolayers (SAMs). These surfaces were analyzed in detail by X-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS) to establish the relationship between the thiol solution composition and the surface composition and structure. We report the use of argon cluster primary ions for the analysis of PEG-thiols, establishing that the different thiols are intimately mixed and that SIMS may be used to measure surface composition of thiol SAMs on gold with a detection limit better than 1% fractional coverage. The adsorption of neutralized chimeric avidin to these surfaces was measured simultaneously using ellipsometry and QCM-D. Comparison of the two measurements demonstrates the expected nonlinearity of the frequency response of the QCM but also reveals a strong variation in the dissipation signal that correlates with the surface density of biotin. These variations are most likely due to the difference in mechanical response of neutralized chimeric avidin bound by just one biotin moiety at low biotin density and two biotin moieties at high density. The transition between the two modes of binding occurs when the average spacing of biotin ligands approaches the diameter of the avidin molecule.
Publisher: American Chemical Society (ACS)
Date: 28-08-2014
DOI: 10.1021/PR500503Q
No related grants have been discovered for Vesa Hytönen.