A potential role for c-jun in cell cycle progression through late G1 and S

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The transcription factor c-Jun/AP-1 is known to mediate cellular responses to receptor signals.
• Previous studies documented early c-jun mRNA accumulation following stimulation.
• The role of c-Jun/AP-1 during specific cell cycle phases remained less understood.

Purpose of the Study:

• To investigate the temporal dynamics of c-jun mRNA accumulation in human fibroblasts.
• To identify novel roles for c-Jun/AP-1 in cell cycle progression.
• To characterize AP-1 DNA binding activity during different cell cycle phases.

Main Methods:

• Quantitative analysis of c-jun mRNA levels in quiescent WI-38 human fibroblasts.
• Gel retardation assays to assess AP-1 DNA binding activity.
• Western blot analysis using anti-Fos antibodies.

Main Results:

• Two distinct peaks of c-jun mRNA accumulation were observed: an early peak (1-5 hours post-stimulation) and a later peak at the G1/S border.
• The late G1/S phase c-jun expression was observed in both quiescent and non-quiescent cells, and in non-human cells.
• AP-1 DNA binding activity was detected in late G1 and S phase nuclear extracts, primarily due to Jun protein.
• Anti-Fos antibodies affected early G1 AP-1 activity but not late G1/S phase activity, suggesting a dissociation of c-Jun from c-Fos.

Conclusions:

• A previously unreported peak of c-jun mRNA occurs at the G1/S border, linked to cell cycle entry into S phase.
• This late G1/S phase AP-1 activity is functionally distinct from early G1 activity, involving c-Jun independent of c-Fos.
• These findings suggest a novel role for c-Jun/AP-1 in regulating mammalian cell cycle progression and growth.