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 γ-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.
Labi
Verena
V
Biocenter, Innsbruck Medical University, Austria. verena.labi@i-med.ac.at
Villunger
Andreas
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004249:DNA Damage; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012542:Scattering, Radiation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C498702:PMAIP1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53