Zac1 functional interactions mediate AP-1 transcriptional activity.

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Zac1 (zinc-finger protein which regulates apoptosis and cell cycle arrest 1) is a transcription factor that binds DNA and regulates apoptosis and cell cycle arrest.
• Zac1 also functions as a transcriptional cofactor for nuclear receptors and p53.
• The specific role of Zac1 in modulating other transcription factors, like Activator protein 1 (AP-1), remains largely unexplored.

Purpose of the Study:

• To investigate the functional role of mouse Zac1 (mZac1) in HeLa cells stimulated with 12-O-tetradecanoylphorbol-13-acetate (PMA), a known AP-1 activator.
• To determine if mZac1 interacts with AP-1 proteins and influences AP-1 transcriptional activity.
• To elucidate Zac1's potential as a coactivator for AP-1.

Main Methods:

• HeLa and HeLa/p53 shRNA cells were treated with PMA to induce AP-1 activity.
• AP-1 activity was measured in the presence and absence of mZac1.
• Physical and functional interactions between mZac1 and AP-1 proteins (c-Jun, c-Fos) were identified.
• AP-1-dependent promoter activities (collagenase, c-Fos, p21(WAF1/Cip1)) were assessed.

Main Results:

• mZac1 prolonged and enhanced PMA-induced AP-1 activity in both cell types.
• Physical and functional interactions were confirmed between mZac1 and AP-1 proteins.
• Zac1 demonstrated coactivator activity for AP-1, as evidenced by the transcriptional activation of AP-1 target genes.

Conclusions:

• Zac1 acts as a selective coactivator for AP-1, enhancing its transcriptional activity.
• The interaction between Zac1 and AP-1 establishes a direct link between these regulatory proteins.
• Zac1 may contribute to AP-1-mediated biological processes, highlighting its significance in gene regulation.