Doklady Biochemistry and Biophysics最新文献

The search for new cytotoxic agents capable of lysing tumor cells is an important task in the fight against cancer. Here we have shown that the HspBP1 protein, the chaperone of the heat shock protein Hsp70, is able to form a complex with the previously discovered peptide (17.1) of the innate immunity protein Tag7. Experiments using thermophoresis demonstrated that the affinity of the Tag7 protein peptide 17.1 to the HspBP1 molecule is 100 times higher than that of the full-sized Tag7 molecule. The addition of the 17.1–HspBP1 complex to tumor cells induces apoptosis and necroptosis in them. The results obtained in this work can be used to develop promising antitumor drugs.

In mammals, the main contribution to the variability of pigmentation is made by two groups of genes directly related to the metabolic pathways of pigment synthesis and controlling the transport of melanosomes in melanocytes to keratinocytes. In order to identify the genetic basis of pigmentation variants, the nucleotide sequences of the melanophilin gene were compared in two groups of ferrets—silver-colored and wild-type animals—using sequencing of 16 exons. In carriers of silver color, a single nucleotide deletion was detected in the 9th exon, leading to a shift in the reading frame and the formation of a stop codon downstream. The protein encoded by the mutant allele is almost completely devoid of the C terminal domain of the protein responsible for the contact of melanosomes with actin during their moving to the periphery of melanocytes, but it retains the leading domain involved in the formation of melanosomes. The combination of the preservation of the N domain and the defect of the C domain of the mutant protein for the first time makes it possible to explain the incomplete dominance of the wild-type protein in heterozygotes.

The PBAF chromatin remodeling complex of the SWI/SNF family plays a critical role in the regulation of gene expression during tissue differentiation and organism development. The subunits of the PBAF complex have domains responsible for binding to N-terminal histone sequences. It determines the specificity of binding of the complex to chromatin. PHF10, a specific subunit of the PBAF complex, contains a DPF domain, which is a unique chromatin interaction domain. A PHF10 isoform that lacks the DPF domain is also present in vertebrate cells. This work shows that during neuronal and muscle differentiation of human and mouse cells, the expression of PHF10 isoforms changes: the form that does not have DPF replaces the form in which it is present. Replacement of PHF10 isoforms in the PBAF complex may affect its selectivity in the regulation of genes in differentiating cells.

Although epigallocatechin-3-gallate (EGCG) can potentiate chemotherapeutic drugs at high concentrations, its clinical translation is hampered by exceeding possible concentration thresholds. This study proposes a dichotomous use of low-concentration EGCG in chemotherapy. During the first cycle of combined treatment with oxaliplatin (OXA), low-concentration EGCG antagonized the cytotoxic effect of OXA on colorectal cancer (CRC) cells. However, when OXA was subsequently administered, the sensitivity of CRC cells markedly increased. Although low-concentration EGCG counteracted OXA, it reduced the OXA-induced secretion of vascular endothelial growth factor by tumor cells, thereby contributing to the increase in the sensitivity of tumor cells to the second round of OXA treatment. Therefore, low-concentration EGCG showed potential as a viable adjunct to modulate chemosensitivity in CRC.

For the first time, N⁶-(5-phenylpentan-1-yl)adenine, a synthetic adenine derivative with a receptor-specific anticytokinin effect, was obtained. This compound exhibits a pronounced anticytokinin effect, reducing cytokinin-induced expression of the GUS reporter gene when interacting with the cytokinin receptor CRE1/AHK4 of the model plant Arabidopsis thaliana. This effect manifests itself much weaker with the related AHK2 receptor and is not observed at all with the AHK3 receptor. We showed that N⁶-(5-phenylpentan-1-yl)adenine does not bind to the ligand-binding sites of the Arabidopsis cytokinin receptors, which does not allow it to be classified as a true cytokinin antagonist. Despite the currently unknown mechanism of action, this compound may find its use as a component of plant growth regulators. Like true anticytokinins, it enhances root growth of Arabidopsis seedlings, apparently suppressing the action of endogenous cytokinins on the “root” receptor CRE1/AHK4.

PHF10 is a subunit of the PBAF complex, which regulates the expression of many genes in developing and maturing organisms. PHF10 has four isoforms that differ in domain structure. The PHF10A isoform, containing a DPF domain at the C-terminus and 46 amino acids at the N-terminus, is necessary for the expression of proliferation genes; the functions of the other isoforms are less studied. In this work, we have established that, upon contact inhibition of mouse and human cell proliferation caused by the establishment of a tight junction and adherence junction between cells, the expression of the PHF10A isoform stops and instead the PHF10D isoform is expressed, which does not contain DPF-domain and N-terminal sequence. The function of the PHF10D isoform may be associated with the establishment of intercellular contacts.