20.500.12556/RUL-137797 Novel insights into biological roles of inducible cAMP early repressor ICER ICER corresponds to a group of alternatively spliced Inducible cAMP Early Repressors with high similarity, but multiple roles, including in circadian rhythm, and are involved in attenuation of cAMPdependent gene expression. We present experimental and in silico data revealing biological differences between the isoforms with exon gamma (ICER) or without it (ICERγ). Both isoforms are expressed in the liver and the adrenal glands and can derive from differential splicing. In adrenals the expression is circadian, with maximum at ZT12 and higher amplitude of Icerγ. In the liver, the expression of Icerγ is lower than Icer in the 24 h time frame. Icer mRNA has a delayed early response to forskolin. The longer ICER protein binds to three DNA grooves of the Per1 promoter, while ICERγ only to two, as deduced by molecular modelling. This is in line with gel shift competition assays showing stronger binding of ICER to Per1 promotor. Only Icerγ siRNA provoked an increase of Per1 expression. In conclusion, we show that ICER and ICERγ have distinct biochemical properties in tissue expression, DNA binding, and response to forskolin. Data are in favour of ICERγ as the physiologically important form in hepatic cells where weaker binding of repressor might be preferred in guiding the cAMP-dependent response. circadian rhythm repressor ICER biological roles ICER ICERγ isoform splicing circadian expression cirkadijski ritem represorja ICER biološka vloga true false true Angleški jezik Slovenski jezik Članek v reviji 2022-07-01 08:15:25 2022-07-01 08:15:32 2022-09-15 04:15:49 0000-00-00 00:00:00 2020 0 0 Str. 396-401 iss. 2 Vol. 530 Sep. 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61 0006-291X 10.1016/j.bbrc.2020.05.017 21943811 1-s2.0-S0006291X20309219-main.pdf 1-s2.0-S0006291X20309219-main.pdf 1 EAEFAFED4DF9D6F2672D5528539AECAB 47dc66b989614fc72c989160943d6a67b6d200e32c1156d669759605a2433a42 014503ce-f906-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=157876 https://www.sciencedirect.com/science/article/pii/S0006291X20309219 1 01dcf411-f905-11ec-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=157875 Medicinska fakulteta 0 0 0