title: Tumor suppression by ARF: gatekeeper and caretaker.
abstract: ARF is a vital tumor suppressor and its loss contributes significantly to cancer. The frequency in which ARF is mutated, deleted or silenced is second to the loss of p53. The most documented and widely accepted activity of ARF is mediated through its activation of the p53 transcriptional program by inhibiting MDM2 function. However, several lines of evidence have surfaced demonstrating that ARF possesses p53-independent functions. One of these p53-independent functions is ARF's regulation of the E2F family. The E2F/DP transcription factor is critical for cell cycle progression. The balance between activator and repressor E2Fs regulates the expression of E2F target genes and thus cell proliferation as well as other cellular functions such as checkpoint, chromosome assembly and repair. Through its ability to bind directly to DP1, ARF can cause dissociation of both activator and repressor E2Fs. While the regulation of the activator E2Fs is related to cell cycle arrest, there is evidence that the regulation of the repressors, E2F4 and E2F5, is significant in maintaining genomic stability.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois College of Medicine, UIC Cancer Center, Chicago, IL USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Dominguez-Brauer
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Brauer
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Julia
authors.initials: J
authors.lastname: Pimkina
authors.forename: Pradip
authors.initials: P
authors.lastname: Raychaudhuri
mesh_terms: D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D050684:E2F Transcription Factors; D016159:Tumor Suppressor Protein p53