PUMA-mediated tumor suppression: A tale of two stories

Several recent studies provided evidence that PUMA, a pro-apoptotic member of the BH3-only protein subgroup of the Bcl-2 family, is critical for restricting survival and recovery of different cell types, including those of the hematopoietic system, after g-irradiation (IR)-triggered DNA damage. According to its pro-apoptotic function downstream of p53, PUMA is considered to act as a tumor suppressor. While this expectation was met in a model of oncogene-driven lymphomagenesis or carcinogen-driven tumor formation in the gut, studies on IR-driven tumor formation revealed surprising new insights into the role of p53-triggered and PUMA-mediated apoptosis in tumorigenesis and stem cell homeostasis.