The p14 subunit of the essential splicing factor 3b (SF3b) can be cross-linked to the branch-point adenosine of pre-mRNA introns within the spliceosome. p14 stably interacts with the SF3b subunit SF3b155, which also binds the 65-kDa subunit of U2 auxiliary splicing factor (U2AF65). We combined biochemical and NMR techniques to study the conformation of p14 either alone or complexed with SF3b155...

The INK4a/ARF locus encodes two distinct tumor suppressors, p16 and p14. Although the contribution of p16 to human tumorigenesis through point mutation, deletion, and hypermethylation has been widely documented, little is known about specific p14 lesions and their consequences. Recent data indicate that p14 suffers inactivation by promoter hypermethylation in colorectal cancer cells. Because it...

The p14/MP1 scaffold complex binds MEK1 and ERK1/2 on late endosomes, thus regulating the strength, duration and intracellular location of MAPK signaling. By organelle proteomics we have compared the protein composition of endosomes purified from genetically modified p14⁻/⁻, p14+/⁻ and p14(rev) mouse embryonic fibroblasts. The latter ones were reconstituted retrovirally from p14⁻/⁻ mouse embryo...

The INK4a/ARF locus encodes two cell cycle-regulatory proteins, p16 and p14, which share an exon using different reading frames. p14 antagonizes MDM2-dependent p53 degradation. However, no point mutations in p14 not altering p16 have been described in primary tumors. We report that p14 is epigenetically inactivated in several colorectal cell lines, and its expression is restored by treatment wi...

Overexpression of E2F-1 induces apoptosis by both a p14-p53and a p73-mediated pathway. p14 is the alternate tumor suppressor product of the INK4a/ARF locus that is inactivated frequently in lung carcinogenesis. Because p14 stabilizes p53, it has been proposed that the loss of p14 is functionally equivalent to a p53 mutation. We have tested this hypothesis by examining the genomic status of the ...

Inactivation of the ARF-p53 tumor suppressor pathway leads to immortalization of murine fibroblasts. The role of this pathway in immortalization of human epithelial cells is not clear. We analyzed the functionality of the p14(ARF)-p53 pathway in human mammary epithelial cells (MEC) immortalized by human papillomavirus 16 (HPV16) E6, the p53 degradation-defective E6 mutant Y54D, or hTERT. E6-MEC...

p14(ARF), the alternative product from the human INK4a/ARF locus, antagonizes Hdm2 and mediates p53 activation in response to oncogenic stimuli. An immunohistochemical study of p14(ARF) expression in 74 samples of aggressive B-cell lymphomas was performed, demonstrating an array of different abnormalities. A distinct nucleolar expression pattern was detected in nontumoral tissue and a subset of...

p14(ARF) is a putative tumor suppressor gene thought to modify the levels of p53. CpG sites within the 5'-flanking region and exon 1beta of p14(ARF) are targets of aberrant methylation and transcriptional silencing in human colorectal cancer (CRC). Here we have developed methylation-specific polymerase chain reaction (MSPCR) methods to detect methylation of CpG sites in p14(ARF) in CRC cell lin...

The present study addressed the impact of human papillomavirus (HPV), p14, and the product of the retinoblastoma gene (pRb) in vulvar carcinoma in relation to other clinicopathologic variables and prognosis. We immunohistochemically studied 217 primary tumors from patients with vulvar carcinoma for the expression of pRb and p14. By the use of in situ hybridization, the primary tumors and 7 lymp...