p19(ARF) is a key regulator of the p53-mediated apoptotic and tumor suppressor pathway. The proapoptotic Bax gene is a transcription target of p53, yet genetic studies in some animal models have suggested that Bax and p53 loss may cooperate in tumorigenesis. ARF-deficient mice are tumor prone, and to determine whether Bax loss could cooperate in the development of these tumors, we generated mic...

The tumour suppressor ARF (alternative reading frame) is encoded by the INK4a (inhibitor of cyclin-dependent kinase 4)/ARF locus, which is frequently altered in human tumours. ARF binds MDM2 (murine double minute 2) and releases p53 from inhibition by MDM2, resulting in stabilization, accumulation and activation of p53. Recently, ARF has been found to associate with other proteins, but, to date...

The p14 alternate reading frame (ARF) tumor suppressor plays a central role in cancer by binding to mdm2 (Hdm2 in humans) and enhancing p53-mediated apoptosis following DNA damage and oncogene activation. It is unclear, however, how ARF initiates its involvement in the p53/mdm2 pathway, as p53 and mdm2 are located in the nucleoplasm, whereas ARF is largely nucleolar in tumor cells. We have used...

BACKGROUND In patients undergoing percutaneous coronary intervention (PCI) in the modern era, the incidence and prognostic implications of acute renal failure (ARF) are unknown. METHODS AND RESULTS With a retrospective analysis of the Mayo Clinic PCI registry, we determined the incidence of, risk factors for, and prognostic implications of ARF (defined as an increase in serum creatinine [Cr] ...

ACUTE RENAL FAILURE (ARF) IN hospitalized patients may be associated with low, normal, or excess extracellular volume, depending on the cause of the ARF, accompanying conditions (eg, heart failure, liver disease), and patterns of administration of crystalloids and colloids. Diuretic agents are frequently given to augment renal salt and water excretion in the setting of extracellular volume over...

The ARF tumor suppressor is part of the CDKN2A locus and is mutated or undetectable in numerous cancers. The best-characterized role for ARF is in stabilizing p53 in response to cellular stress. However, ARF has tumor suppressive functions outside this pathway that have not been fully defined. Primary mouse embryonic fibroblasts (MEFs) lacking the ARF tumor suppressor contain abnormal numbers o...

Abstract We investigated outcomes for patients born after 1983 and hospitalized with initial acute rheumatic fever (ARF) in New Zealand during 1989–2012. linked ARF progression outcome data (recurrent hospitalization ARF, heart disease [RHD], death from circulatory causes) 1989–2015. Retrospective analysis identified RHD <40 years of age who were 2010–2015 previously ARF. Most (86.4%) the 2,182...

Induction of the Arf tumor suppressor gene by elevated thresholds of mitogenic signals activates a p53-dependent transcriptional response that triggers either growth arrest or apoptosis, thereby countering abnormal cell proliferation. Conversely, Arf inactivation is associated with tumor development. Expression of Arf in tissues of adult mice is difficult to detect, possibly because its inducti...

The tumour suppressor protein ARF provides a defence mechanism against hyperproliferative stresses that can result from the aberrant activation of oncogenes. Accordingly, ARF is silenced or deleted in many human cancers. Activation of ARF can arrest growth and cell cycle progression, or trigger apoptosis. A principle mediator of these effects is p53, which ARF stabilizes by binding and inhibiti...

Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is involved in the pathogenesis of MYC...