Abstract
EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications. Here we describe the identification of a splicing isoform for the human EGR1 gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.
Highlights
Growth response protein 1 (EGR1) is a zinc finger transcription factor encoded by gene mapping on the human chromosome 5 and consisting of two exons
It has been shown that Early growth response protein 1 (EGR1) can interact with yes associated protein 1 (YAP-1) through a PPxY motif within the region lacking in the new isoform
The region lacking in the EGR1 isoform contains Lysine 272 that is involved in the sumoylation process and in several phosphorylation sites, suggesting that the described isoform may possess differing stability and activity compared to the canonical EGR1
Summary
Growth response protein 1 (EGR1) is a zinc finger transcription factor encoded by gene mapping on the human chromosome 5 and consisting of two exons. The hyperphosphorylation of EGR1 by the protein kinase, casein kinase II (CKII), has a negative effect on its DNA-binding and transcriptional activity [41] It suggests that the phosphorylated form of EGR1 plays distinct roles in cellular physiology [42] and the phosphorylation/dephosphorylation process may serve as a molecular switch for restricting the function of EGR1 as a transcription factor [43]. Both in mouse and human, EGR1 is regulated at a post-transcriptional level by alternative polyadenylation, a mechanism that generates two EGR1 mRNA variants differing for a potential N-methyl-D-aspartate receptor (NMDA-R)-responsive Carboxypeptidase E (CPE) sequence [44,45]. Our report shows the identification and characterization of a splicing event involving the EGR1 gene transcript that clearly removes a region in the coding sequence of the second exon, strongly affecting the EGR1 transcriptional activation property
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