Protein kinase B (Akt)-mediated cAMP response element-binding protein (CREB) activation of cyclin D1 gene transcription (No standard abbreviation exists for this composite pathway.)

This pathway or network involves the phosphorylation of CREB by Akt, a serine/threonine kinase, which increases CREB’s activity as a transcription factor. CREB then binds to CRE sites within the promoter region of the cyclin D1 gene, driving its transcription and subsequent cell cycle progression. Dysregulation of Akt- and CREB-mediated cyclin D1 activation is implicated in tumorigenesis, particularly in prostate and breast cancer, and is associated with cell proliferation, resistance to chemotherapeutic agents, and altered cellular metabolism. Therapeutic intervention typically targets Akt or CREB individually, not the composite pathway, to inhibit their pro-proliferative and anti-apoptotic activities.

Other names

Akt signaling pathwayPI3K/Akt/CREB/cyclin D1 axisCREB-dependent cyclin D1 transcription

Inhibition of Akt blocks downstream phosphorylation of CREB, reducing cyclin D1 expression and cell proliferation. Inhibition of CREB phosphorylation prevents the transcriptional activation of pro-proliferative genes including cyclin D1. Some drugs downregulate cyclin D1 directly, thereby limiting G1/S cell cycle progression.