ID4: a new player in the cancer arena

Id proteins (Id-1 to 4) are dominant negative regulators of basic helix-loop-helix transcription factors. They play a key role during development, preventing cell differentiation while inducing cell proliferation. They are poorly expressed in adult life but can be reactivated in tumorigenesis. Several evidences indicate that Id proteins are associated with loss of differentiation, unrestricted proliferation and neoangiogenesis in diverse human cancers. Recently, we identified Id4 as a transcriptional target of the protein complex mutant p53/E2F1/p300 in breast cancer. Id4 protein binds, stabilizes and enhances the translation of mRNAs encoding proangiogenic cytokines, such as IL8 and GRO-alpha, increasing the angiogenic potential of cancer cells. We present here an overview of the current experimental data that links Id4 to cancer. We provide evidence also of the induction of Id4 following anticancer treatments in mutant p53-carrying cells. Indeed, mutant p53 is recruited to a specific region of the Id4 promoter upon DNA damage. Our findings indicate that Id4, besides its proangiogenic role, might also participate in the chemoresistance associated to mutant p53 proteins exerting gain of function activities.