Playing both sides: nucleophosmin between tumor suppression and oncogenesis.
Nucleophosmin (NPM) is frequently mutated in acute myeloid leukemias and is thought to act as both a proto-oncogene and a tumor suppressor. Although genetic and molecular evidence has shed light on the mechanisms of NPM-mediated tumor suppression, the potential role of NPM mutants as oncogenes remains ill defined. Now, new data provide a straightforward mechanism for this latter function, as NPM is shown to regulate the stability and the function of MYC. Remarkably, the same leitmotif of "placing a critical cell regulator in the wrong place at the wrong time" appears to underscore all the cancer-promoting activities of mutated NPM.
Di Fiore
Pier Paolo
PP
Istituto FIRC di Oncologia Molecolare (IFOM), 20139 Milan, Italy. pierpaolo.difiore@ifom-ieo-campus.it
D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism; D044783:F-Box Proteins / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D044783:F-Box Proteins; C000715470:MAS1 protein, human; D050505:Mutant Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000090243:Nucleophosmin