K Protein (k + protein)

Distribution by Scientific Domains

Selected Abstracts

Increased expression of the heterogeneous nuclear ribonucleoprotein K in pancreatic cancer and its association with the mutant p53

Renyuan Zhou
Abstract The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction including DNA transcription, RNA splicing, RNA stability and translation. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. In this study, we investigated the altered protein expression and the subcellular distribution of the hnRNP K protein using tissue microarrays in pancreatic cancer. We showed an increased cytoplasmic hnRNP K in pancreatic cancer. This increase in hnRNP K protein occurs at the posttranscriptional level. We postulate that the cytoplasmic accumulation of hnRNP K will lead to silenced mRNA translation of tumor suppressor genes and thus contributes to pancreatic cancer development. We also demonstrated that knocking down of hnRNP K expression by siRNA inhibited pancreatic cancer cell growth and colony formation. hnRNP K was identified as a member of the p53/HDM2 pathway. Whether hnRNP K interacts with the mutant p53 is not known. Using two different pancreatic cancer cell lines, we can demonstrate that hnRNP K interacts with the mutant p53. The subcellular distribution and function of the mutant p53 and the interaction of hnRNP K/mutant p53 were affected by the Ras/MEK/ERK pathway, growth factors and the specific p53 mutations in pancreatic cancer cells. Since Kras is activated and p53 is mutated in most pancreatic cancers, these data unveiled an important new signaling pathway that linked by hnRNP K and mutant p53 in pancreatic cancer tumorigenesis. [source]

Landscape of the hnRNP K protein,protein interactome

Micha, Mikula
Abstract The heterogeneous nuclear ribonucleoprotein K is an ancient RNA/DNA-binding protein that is involved in multiple processes that compose gene expression. The pleiotropic action of K protein reflects its ability to interact with different classes of factors, interactions that are regulated by extracellular signals. We used affinity purification and MS to better define the repertoire of K protein partners. We identified a large number of new K protein partners, some typically found in subcellular compartments, such as plasma membrane, where K protein has not previously been seen. Electron microscopy showed K protein in the nucleus, cytoplasm, mitochondria, and in vicinity of plasma membrane. These observations greatly expanded the view of the landscape of K protein,protein interaction and provide new opportunities to explore signal transduction and gene expression in several subcellular compartments. [source]

The presence of aberrant DNA methylation in noncancerous esophageal mucosae in association with smoking history

CANCER, Issue 15 2009
A target for risk diagnosis, prevention of esophageal cancers
Abstract BACKGROUND: Esophageal squamous cell carcinomas (ESCCs) tend to have multiple primary lesions, and it is believed that they arise from background mucosae with accumulation of genetic/epigenetic alterations. In this study, the objective was to elucidate the effects of smoking and drinking on the accumulation of epigenetic alterations in background mucosae. METHODS: Genes that are silenced in human ESCCs were searched for by treating 3 ESCC cell lines with the demethylating agent, 5-aza-2,-deoxycytidine and performing oligonucleotide microarrays. Methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction analysis of 60 ESCCs and their corresponding background mucosae. RESULTS: Forty-seven genes were identified as methylation-silenced in at least 1 of the 3 ESCC cell lines, and 14 of those genes (claudin 6 [CLDN6]; G protein-coupled receptor 158 [GPR158]; homeobox A9 [HOXA9]; metallothionein 1M [MT1M]; neurofilament, heavy polypeptide 200 kDa [NEFH]; plakophilin 1 [PKP1]; protein phosphatase 1, regulatory [inhibitor] subunit 14A [PPP1R14A]; pyrin domain and caspase recruitment domain containing [PYCARD]; R-spondin family, member 4 [RSPO4]; testis-specific protein, Y-encoded,like 5 [TSPYL5]; ubiquitin carboxyl-terminal esterase L1 [UCHL1]; zinc-finger protein 42 homolog [ZFP42]; zinc-finger protein interacting with K protein 1 homolog [ZIK1]; and zinc-finger and SCAN domain containing 18 [ZSCAN18]) were used as markers. In the background mucosae, methylation levels of 5 genes (HOXA9, MT1M, NEFH, RSPO4, and UCHL1) had significant correlations with smoking duration (, = .268; P = .044; , = .405; P = .002; , = .285; P = .032; , = .300; P = .024; and , = .437; P = .001, respectively). In contrast, an inverse correlation between PYCARD methylation levels and alcohol intake was observed (, = ,.334, P = .025) among individuals with the inactive aldehyde dehydrogenase 2 (ALDH2) genotype. CONCLUSIONS: The current results suggested that ESCCs developed from an epigenetic field for cancerization, which was induced by exposure to carcinogenic factors, such as tobacco smoking. The epigenetic field defect will be a novel target for risk diagnosis and prevention of ESCCs. Cancer 2009. 2009 American Cancer Society. [source]