Inhibition of c-jun causes reversible proliferative arrest and withdrawal from the cell cycle

Abstract

We studied the effect of c-jun depletion in Friend murine erythroleukemia (F-MEL) cells stably transfected with a plasmid that allowed for the glucocorticoid-mediated conditional expression of c-jun antisense sequences. The c-jun cDNA used for the construction of the vector was modified so as to prevent the nonspecific targeting of junB and junD transcripts. High level and rapid induction of c-jun antisense transcripts was achieved with as little as 10(-8) mol/L dexamethasone (DEX) and resulted in a 80% to 90% reduction in c-jun protein levels. The continuous exposure of the transfected cells to DEX inhibited growth by greater than 85% over a 5-day period, whereas DEX had no effect on the growth rate of control F-MEL cells. This proliferative block was associated with a reversible accumulation of cells with a 2n DNA content. When these cells were recultured in the absence of DEX, c- jun protein rapidly reappeared and the immediate early response genes egr-1, junB, and c-myc were transiently expressed. Thus, inhibition of c-jun protein causes logarithmically growing cells to leave the cell cycle and to enter a state closely resembling, if not identical to, G0. These results underscore the importance of c-jun in maintaining cellular proliferation and provide additional evidence for the participation of proto-oncogenes in cell cycle control.

Fukutin Protein Participates in Cell Proliferation by Enhancing Cyclin D1 Expression through Binding to the Transcription Factor Activator Protein-1: An In Vitro Study

“…JNK catalyzes the conversion of c-Jun to p-c-Jun, which enables AP-1 to increase the affinity to CREBBP and the transcription activity [34][35][36]. Concretely, it has been shown that phosphorylation of c-Jun at serine 63/73 residues is required for transcriptional activation of cyclin D1 [37]. This is supported by our finding that JNK inhibitor treatment resulted in the downregulation of cyclin D1 expression.…”

Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases

“…More than that, the cell contains large concentrations of macromolecules (up to 400 g/L), among which are proteins, nucleic acids, lipids, glycans, and solvated ions [ 118 ], which suggests that approximately 40% of the cell volume can be occupied by macromolecules and become physically inaccessible to other molecules. Accordingly, it can be assumed that crowding conditions affect both the kinetics and thermodynamics of interactions between macromolecules, including protein folding and aggregation [ 119 , 120 , 121 ]. Since crowding has a strong effect on protein–protein interactions, its influence on the conformation and self-association of chaperones, interaction of chaperones with target proteins, and the aggregation of the target proteins should also be taken into account [ 122 ].…”