We have previously shown that extracellular vesicles secreted by metastatic melanoma cells stimulate the growth, migration, and stemness of normal keratinocytes. This study showed for the first time ...that extracellular vesicles secreted by the metastatic melanoma cell lines mel H, mel Kor, and mel P contain, both at the mRNA and protein levels, the 7-type nicotinic acetylcholine receptor (7-nAChR), which is involved in the regulation of the oncogenic signaling pathways in epithelial cells. Incubation with the vesicles secreted by mel H cells and containing the highest amount of mRNA coding 7-nAChR increased the surface expression of 7-nAChR in normal Het-1A keratinocytes and stimulated their growth. Meanwhile, both of these effects disappeared in the presence of -bungarotoxin, an 7-nAChR inhibitor. A bioinformatic analysis revealed a correlation between the increased expression of the CHRNA7 gene coding 7-nAChR in patients with metastatic melanoma and a poor survival prognosis. Therefore, extracellular vesicles derived from metastatic melanoma cells can transfer mRNA coding 7-nAChR, thus enhancing the surface expression of this receptor and stimulating the growth of normal keratinocytes. Targeting of 7-nAChR may become a new strategy for controlling the malignant transformation of keratinocytes.
The Role of Linker Histones in Carcinogenesis Lyubitelev, A. V.; Kirpichnikov, M. P.; Studitsky, V. M.
Russian journal of bioorganic chemistry,
2021/1, Letnik:
47, Številka:
1
Journal Article
Recenzirano
—
Linker histones are DNA-binding architectural chromatin proteins involved in the formation of supranucleosomal levels of chromatin packaging. In mammals, 11 variants of these proteins are known, ...but the functional significance of this diversity is currently not fully defined. In addition to the main structural function, linker histones are involved in regulatory interactions, such as global gene deregulation during carcinogenesis. In turn, these changes in carcinogenesis can affect both linker histones through mutations of their encoding genes or changes in the expression of these genes, and the regulatory systems of the cell, causing a redistribution of linker histone variants in interphase chromatin, disrupting their posttranslational modifications or forming functionally active complexes with them. In some cases, changes in the metabolism of linker histones could be a possible cause of malignant transformation, as well as act as possible prognostic markers. Possible mechanisms of such changes in carcinogenesis are discussed, which also allow us to better understand the functions of linker histone variants and domains of these proteins in normal cells.
Axionlike particles a (ALPs) that couple to the Standard Model gauge fields could be observed in the high-energy photon scattering γN → Na off nuclei followed by the a → γ γ decay. In the present ...paper we describe the calculation of the ALP production cross section and the properties of this production. The cross section formulas are implemented in the program for the simulation of events in the NA64 experiment, the active electron beam dump facility at the CERN Super Proton Synchrotron. We study the prospects of the NA64 experiment to search for ALP in the 10 MeV ≲ ma ≲ 100 MeV mass range for the statistics corresponding to up to 5 × 1012 electrons on target.
We investigated the epitope specificity of different monoclonal antibodies recognizing the cancer testis antigen PRAME. Antibody 5D3 binds to the fragment of PRAME corresponding to 160–180 amino acid ...residues. Antibodies 6H8 and F11 bind to the fragment corresponding to 180–200 amino acid residues of PRAME. These antibodies retained the ability to recognize these PRAME fragments after chimerization.
Poly(ADP-ribosyl)ation plays a key role in cellular metabolism. Covalent poly(ADP-ribosyl)ation affects the activity of the proteins engaged in DNA repair, chromatin structure regulation, gene ...expression, RNA processing, ribosome biogenesis, and protein translation. Non-covalent PAR-dependent interactions are involved in the various types of cellular response to stress and viral infection, such as inflammation, hormonal signaling, and the immune response. The review discusses how structurally different poly(ADP-ribose) (PAR) molecules composed of identical monomers can differentially participate in various cellular processes acting as the so-called PAR code. The article describes the ability of PAR polymers to form functional biomolecular clusters through a phase-separation in response to various signals. This phase-separation contributes to rapid spatial segregation of biochemical processes and effective recruitment of the necessary components. The cellular PAR level is tightly controlled by a network of regulatory proteins: PAR code writers, readers, and erasers. Impaired PAR metabolism is associated with the development of pathological processes causing oncological, cardiovascular, and neurodegenerative diseases. Pharmacological correction of the PAR level may represent a new approach to the treatment of various diseases.
Structure and functions of linker histones Lyubitelev, A. V.; Nikitin, D. V.; Shaytan, A. K. ...
Biochemistry (Moscow),
03/2016, Letnik:
81, Številka:
3
Journal Article
Recenzirano
Linker histones such as variants H1, H5, and other similar proteins play an important role in regulation of chromatin structure and dynamics. However, interactions of linker histones with DNA and ...proteins, as well as specific functions of their different variants, are poorly studied. This is because they acquire tertiary structure only when interacting with a nucleosome, and because of limitations of currently available methods. However, deeper investigation of linker histones and their interactions with other proteins will address a number of important questions — from structure of compacted chromatin to regulation of early embryogenesis. In this review, structures of histone H1 variants and its interaction with chromatin DNA are considered. A possible functional significance of different H1 variants, a role of these proteins in maintaining interphase chromatin structure, and interactions of linker histones with other cellular proteins are also discussed.
Two monoclonal antibodies recognizing non-overlapping epitopes of the PRAME protein were injected into immunocompetent mice to study their influence on the growth of subcutaneous tumor nodes. The ...B16F10 murine melanoma line, either expressing human PRAME protein or bearing only a vector without
PRAME
gene, were used as transplants. Each of the antibodies showed the ability to suppress tumor growth of a PRAME-expressing tumour, but not a tumor without PRAME.
Photochemical reaction dynamics of the primary events in recombinant bacteriorhodopsin (bR
rec
) was studied by femtosecond laser absorption spectroscopy with 25-fs time resolution. bR
rec
was ...produced in an Escherichia coli expression system. Since bR
rec
was prepared in a DMPC–CHAPS micelle system in the monomeric form, its comparison with trimeric and monomeric forms of the native bacteriorhodopsin (bR
trim
and bR
mon
, respectively) was carried out. We found that bR
rec
intermediate I (excited state of bR) was formed in the range of 100 fs, as in the case of bR
trim
and bR
mon
. Further processes, namely the decay of the excited state I and the formation of intermediates
J
and
K
of bR
rec
, occurred more slowly compared to bR
trim
, but similarly to bR
mon
. The lifetime of intermediate
I
, judging from the signal of Δ
A
ESA
(470-480 nm), was 0.68 ps (78%) and 4.4 ps (22%) for bR
rec
, 0.52 ps (73%) and 1.7 ps (27%) for bR
mon
, and 0.45 ps (90%) and 1.75 ps (10%) for bR
trim
. The formation time of intermediate
K
, judging from the signal of Δ
A
GSA
(625-635 nm), was 13.5 ps for bR
rec
, 9.8 ps for bR
mon
, and 4.3 ps for bR
trim
. In addition, there was a decrease in the photoreaction efficiency of bR
rec
and bR
mon
as seen by a decrease in absorbance in the differential spectrum of the intermediate K by ~14%. Since photochemical properties of bR
rec
are similar to those of the monomeric form of the native protein, bR
rec
and its mutants can be considered as a basis for further studies of the mechanism of bacteriorhodopsin functioning.
Objective:
Wound healing is a complex process based on the regulation of proliferation and migration of epithelial cells. Chronic wounds are characterized by increased proliferation and decreased ...epidermal cell migration. The human secreted protein SLURP-2 regulates the growth and differentiation of epithelial cells. It was previously shown that the targets of SLURP-2 are nicotinic acetylcholine receptors (nAChRs) of different types, as well as muscarinic acetylcholine receptors involved in the regulation of epithelial cell homeostasis.
Methods:
In this study, we investigated the effect of a recombinant analog of the human protein SLURP-2 and its mutant variants on viability and migration of oral keratinocytes in a wound healing test. The findings were analyzed in comparison with the effect of proteins on the ionotropic activity of the α7-nAChR channel expressed in
Xenopus laevis
oocytes.
Results and Discussion:
In this work, we found that acceleration of keratinocyte migration upon incubation with SLURP-2 is mediated by α7-nAChR. Using alanine scanning mutagenesis, we showed that the R20A mutation of the SLURP-2 molecule enhances the inhibitory activity of SLURP-2 toward α7-nAChR and leads to a greater stimulation of Het-1A keratinocyte migration and suppresses the proliferation of Het-1A cells. At the same time, other SLURP-2 mutations inhibit α7-nAChR and reduce the proliferation and migration of keratinocytes.
Conclusions:
New information about the epitopes of the SLURP-2 molecule, the replacement of which can lead to a targeted change in the biological activity of SLURP-2 was obtained. Further study of ability of regulation of SLURP-2 activity may be useful for a design of new drugs that stimulate wound healing.
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