Tag Archives: transcriptional regulation

Role of PARP and protein poly-ADP-ribosylation process in regulation of cell functions

V. R. Drel1, I. O. Shymanskyy2, N. О. Sybirna1, M. M. Veliky2

1Ivan Franko National University of Lviv, Ukraine;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: drelvictor@gmail.com; ishymansk@inbox.ru

This review focuses on the biological role of enzymes involved in posttranslational modification of proteins by their poly-ADP-ribosylation, a NAD-consuming process with an emerging key role in providing fundamental cell functions. To this end, detailed analysis of structural organization in relation to basic functions of the poly(ADP-ribose)polymerase-1 (PARP-1), the founding member of the PARP family, and other poly(ADP-ribose)polymerase isoforms is presented here. These include the current views on the role of PARP family enzymes and processes of poly-ADP-ribosylation of proteins in chromatin structure remodeling, DNA damage repair, regulation of gene expression, and integration of cellular signaling pathways. Considerable attention is paid to the involvement of PARP in cellular functions, particularly in cell division, intracellular transport of macromolcules, proteasomal protein degradation, immune response and caspase-independent necrotic pathways defined as necroptosis (programmed necrosis). In the light of the remarkable successes that have been reported for treating inflammatory disorders and cancer with different classes of PARPs inhibitors, we discuss the prospects of targeting PARPs with therapeutic purposes.

Transcriptional regulation of NOX genes expression in human breast adenocarcinoma MCF-7 cells is modulated by adaptor protein Ruk/CIN85

A. V. Bazalii, I. R. Horak, G. V. Pasichnyk, S. V. Komisarenko, L. B. Drobot

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: drobot@biochem.kiev.ua

NADPH oxidases are key components of redox-dependent signaling networks involved in the control of cancer cell proliferation, survival and invasion. The data have been accumulated that demonstrate specific expression patterns and levels of NADPH oxidase homologues (NOXs) and accessory genes in human cancer cell lines and primary tumors as well as modulation of these parameters by extracellular cues. Our previous studies revealed that ROS production by human colorectal adenocarcinoma HT-29 cells is positively correla­ted with adaptor protein Ruk/CIN85 expression while increased levels of Ruk/CIN85 in weakly invasive human breast adenocarcinoma MCF-7 cells contribute to their malignant phenotype through the constitutive activation of Src/Akt pathway. In this study, to investigate whether overexpression of Ruk/CIN85 in MCF-7 cells can influence transcriptional regulation of NOXs genes, the subclones of MCF-7 cells with different levels­ of Ruk/CIN85 were screened for NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 as well as for regulatory subunit p22Phox mRNA contents by quantitative RT-PCR (qPCR). Systemic multidirectional changes in mRNA levels for NOX1, NOX2, NOX5, DUOX2 and p22Phox were revealed in Ruk/CIN85 overexpressing cells in comparison to control WT cells. Knocking down of Ruk/CIN85 using technology of RNA-interference resulted in the reversion of these changes. Further studies are necessary to elucidate, by which molecular mechanisms Ruk/CIN85 could affect transcriptional regulation of NOXs genes.