The p14(ARF)-MDM2-p53 pathway constitutes an effective mechanism for protecting cells from oncogenic stimuli such as activated Ras and Myc. Importantly, Ras activation induces p14(ARF) and often occurs earlier than p53 inactivation during cancer development. Here, we show that RUNX3, a tumor suppressor in various tumors including stomach, bladder, colon, and lung, is stabilized by Ras activatio...

Although numerous linear motifs that direct protein trafficking within cells have been identified, there are few examples of linear sorting signals mediating directed export of membrane proteins from the Golgi complex to the plasma membrane. The reovirus fusion-associated small transmembrane proteins are simple, single-pass transmembrane proteins that traffic through the endoplasmic reticulum-G...

A cytoplasmic polypeptide with a molecular weight of 14,000 (p14) was previously found to be the principal covalent target protein of the carcinogen, N-2-fluorenylacetamide (2-acetylaminofluorene), early during carcinogenesis in rat liver. The level of immunodetected p14 was markedly increased specifically during all stages of mitosis of hepatocytes in normal and regenerating partially hepatect...

We have previously detected a large germ-line deletion, which included the entire p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster, in the largest melanoma-neural system tumor (NST) syndrome family known to date by means of heterozygosity mapping based on microsatellite markers. Here, we used gene dose mapping with sequence-tagged site real-time PCR to locate the deletion end points, which were then ...

Murine double minute clone 2 (MDM2), p14 alternate reading frame (p14arf), and nucleophosmin (NPM) regulate p53 activity. A total of 200 biopsies, including normal bronchial, pre-invasive and invasive tissues, were examined for changes in NPM, p14arf, MDM2 and p53 expression patterns by immunohistochemistry and immunofluorescence with confocal microscopy. NPM and p14arf displayed a diffuse nucl...

Hepatitis C virus (HCV) chronic infections represent one of the major and still unresolved health problems because of low efficiency and high cost of current therapy. Therefore, our studies centered on a viral protein, the NS3 helicase, whose activity is indispensable for replication of the viral RNA, and on its peptide inhibitor that corresponds to a highly conserved arginine-rich sequence of ...

To elucidate the role of p53/p16/RB1 pathways in the tumorigenesis of primary central nervous system lymphomas (PCNSLs), we have analyzed p14, p16, RB1, p21, and p27 status in a series of their 18 sporadic cases of diffuse large B-cell lymphoma, using methylationspecific PCR, differential PCR, and immunohistochemistry. Homozygous deletion or methylation of p14 was detected in 10 (56%) PCNSLs, a...

The von Hippel-Lindau disease (VHL) gene is a novel tumor suppressor gene that plays a role in the pathogenesis of renal cell carcinomas and hemangioblastomas of the central nervous system. To begin an evaluation of the biological functions of the VHL gene product (pVHL), we prepared bacterial fusion protein between glutathione S-transferase and wild-type or mutant pVHLs. The fusion proteins we...