p53 upregulated modulator of apoptosis (PUMA)

PUMA (p53 upregulated modulator of apoptosis), also known as Bcl-2-binding component 3 (BBC3), is a pro-apoptotic protein and a member of the Bcl-2 family, specifically classified within the BH3-only subgroup. It plays a critical role in regulating apoptosis in response to various cellular stresses. PUMA serves as a proximal signaling molecule that transduces apoptotic signals—primarily from genotoxic stress or cytokine/growth factor withdrawal—to mitochondria. Its ablation leads to resistance against various apoptotic stimuli and contributes to cancer development or therapeutic resistance. A unique feature of PUMA’s mechanism involves “double-bolt locking” anti-apoptotic proteins through both its BH3 domain and CTS—a property conferring resistance against certain small-molecule inhibitors (“BH3 mimetics”).

Other names

Bcl-2-binding component 3BBC3

Antagonizes antiapoptotic Bcl-2 family proteins, releasing Bax/Bak to induce apoptosis.