Publication

Coupled and uncoupled induction of fos and jun transcription by different second messengers in cells of hematopoietic origin

Johan Auwerx
1990
Journal paper
Abstract

The nuclear oncoproteins fos and jun are associated as a heterodimer which binds to TPA (PMA or TPA: phorbol 12-myristate 13-acetate)- responsive promoter elements (TRE), the recognition site for the transcription factor AP-1. The fos/jun heterodimer has a higher affinity to the TRE and stimulates transcription of responsive genes more than the jun homodimer. The association of these two oncoproteins may play a central role in signal transduction and regulation of cell proliferation and differentiation. We further defined the regulation of fos and jun by studying their inducibility by second messengers in cells of hematopoietic origin. In THP-1 monocytic leukemia cells fos and jun mRNA levels are regulated in a coupled manner by second messengers activated after membrane phospholipid turnover. Addition of phospholipase C to cells, as well as stimulation of protein kinase C and release of intracellular Ca2+, caused a rapid induction of fos and jun mRNA levels, but the induction of jun mRNA showed a more persistant and less transient pattern than fos. In contrast to the phosphoinositol system, stimulation of the adenylate cyclase pathway in THP-1 cells induced only fos transcription whereas jun mRNA levels remained unchanged. A similar uncoupling of fos and jun inducibility was found after phorbol ester addition to the human erythroleukemia cell line HEL and the human promyelocytic cell line HL-60. The uncoupling of fos and jun levels might predispose cells to the formation of combinatorial transcription complexes of a different composition and activity than the fos/jun heterodimer. Indeed, nuclear extracts from THP-1 cells before or after activation of the phosphinositol or adenylate cyclase second messenger pathways revealed a correlation in fos and jun expression and specific binding of the heterocomplex to a TRE sequence.

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Related concepts (35)
Transcription factor Jun
Transcription factor Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun (). The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ju-nana, the Japanese word for 17.
Transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism.
Signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Most commonly, protein phosphorylation is catalyzed by protein kinases, ultimately resulting in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.
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