2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 54(2020) N 5 p. 749-756; DOI 10.1134/S0026893320050076 Full Text

A.I. Melnikova1,2, T.S. Krasnova1, N.A. Zubkova3, A.N. Tiulpakov3, P.M. Rubtsov1*

Alternative Variants of Pax4 Human Transcription Factor: Comparative Transcriptional Activity

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow oblast, 141701 Russia
3Endocrinology Research Centre, Moscow, 117036 Russia

Received - 2020-04-21; Revised - 2020-04-21; Accepted - 2020-04-27

MODY is a group of genetically and clinically heterogeneous forms of diabetes characterized by auto-somal dominant inheritance and is subdivided in 13 subtypes dependent on the gene involved. The subtype MODY9 is a very rare form caused by mutations in the gene encoding the PAX4 transcription factor which is engaged in differentiation of pancreatic beta-cells. PAX4 contains two DNA-binding domains-Paired and Homeo. Expression of the human PAX4 gene is tissue-specific. The alternatively spliced mRNA variants encode for protein isoforms which differ within their N- and C-terminal regions. In this study, the transcriptional activities of the human PAX4 variants, both known and new ones, were determined. The full-length PAX4 containing intact DNA-binding domains was found to have maximal activity in transient expression system of the firefly luciferase reporter gene under control of the insulin promoter in HEK293 cells. The transcriptional activity is significantly reduced in the variants lacking eight N-terminal amino acid residues and/or variants whose Homeo domain is truncated from the C-terminus. Similar data were obtained with the glucagon promoter reporter system. The aberrant PAX4 variants were shown to retain stability and nuclear localization.

transcription factors, PAX4, monogenic diabetes MODY, MODY9, transcriptional activity, insulin gene promoter, glucagon gene promoter