Translational regulation mechanisms of AP-1 proteins.
The activator protein 1 (AP-1) transcription factor is assembled from jun-jun, jun-fos, or jun-atf family protein homo- or heterodimers. AP-1 belongs to the class of basic leucine zipper (bZIP) transcription factors. It binds to promoters of its target genes in a sequence-specific manner, and transactivates or represses them. AP-1 proteins are implicated in the regulation of a variety of cellular processes including proliferation and survival, differentiation, growth, apoptosis, cell migration, and transformation. The decision if a given AP-1 factor is positively or negatively regulating a specific target gene is made upon abundance of dimerization partners, dimer-composition, post-translational regulation, and interaction with accessory proteins. In this review we describe translational control mechanisms that can regulate the abundance of AP-1 proteins. The Atf4/5, and JunD (mRNAs) are regulated by upORF dependent mechanisms. JUNB (mRNA) translation is controlled via mTOR. Translation efficiency of the unstable c-Fos (mRNA) can be decreased by the miRNA mir7B, while its perinuclear translation might facilitate efficient nuclear c-fos protein import. c-Jun (mRNA) appears to be regulated by both, m7G cap (CAP)-dependent and CAP-independent translational control mechanisms, via putative internal ribosome entry segments (IRES). IRES elements were also proposed to play a role in the regulation of JunD (mRNA). We conclude that in addition to transcriptional and post-translational control mechanisms translational regulation contributes to the balanced production of AP-1 proteins, in order to maintain physiological cellular conditions.
Vesely
Paul Willi
PW
Institute for Pathology, Auenbruggerplatz 25, A-8036 Graz, Austria. paul.vesely@klinikum-graz.at
Staber
Philipp Bernhard
PB
Hoefler
Gerald
G
Kenner
Lukas
L
D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D014176:Protein Biosynthesis; D039381:RNA Cap-Binding Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
D035683:MicroRNAs; D039381:RNA Cap-Binding Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors