PUMA (p53 upregulated modulator of apoptosis), also known as Bbc3 (Bcl-2-binding component 3), is a critical mediator of p53-dependent and -independent apoptosis []. PUMA transduces death signals primarily to the mitochondria. It is induced in cells after p53 activation. It binds to Bcl-2, localises to the mitochondria to induce cytochrome c release, and activates the rapid induction of apoptosis []. PUMA is capable of inhibiting all the five major anti-apoptotic Bcl-2-like proteins (Mcl-1, Bcl-2, Bcl-XL, Bcl-W and A1) []. The binding of PUMA to the inhibitory members of the Bcl-2 family via its BH3 domain results in the displacement of the proteins Bax and/or Bak, and seems to be a critical regulatory step in the induction of apoptosis [].
