Bcl-2-binding component 3 (BBC3)

Bcl-2-binding component 3 (BBC3), commonly known as PUMA (p53 upregulated modulator of apoptosis), is a pro-apoptotic member of the Bcl-2 family of proteins. Unlike multi-domain Bcl-2 proteins, PUMA is a BH3-only protein, meaning it contains only the BH3 domain required for interaction with other Bcl-2 family members and lacks the other BH domains[3]. PUMA is intrinsically unstructured in solution but folds into an alpha helix upon binding to its partners[3]. It is induced in response to cellular stress and DNA damage, particularly via the tumor suppressor p53, and functions as a critical mediator of apoptosis by binding to and neutralizing anti-apoptotic Bcl-2 family members, thereby promoting mitochondrial outer membrane permeabilization (MOMP), cytochrome c release, and activation of the intrinsic apoptotic pathway[3][6]. PUMA is considered a potential drug target due to its central role in apoptosis regulation and its implication in cancer, where dysregulation of apoptosis contributes to tumorigenesis[5]. However, while the Bcl-2 family in general has been targeted therapeutically, there are no FDA-approved drugs specifically targeting PUMA at this time. Its physiological and pathological roles are primarily associated with p53-mediated apoptosis and cancer, and it also participates in broader stress response pathways[3][6].

Other names

PUMA (p53 upregulated modulator of apoptosis)Bcl-2-binding protein 3Bbc3

For drugs targeting PUMA, mechanism is not specified in the search results, but BH3-mimetic drugs targeting Bcl-2 family proteins generally work by binding the BH3 domain of anti-apoptotic proteins, thereby releasing pro-apoptotic BH3-only proteins like PUMA to induce apoptosis.