Dataset Information

Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein.

ABSTRACT: C19ORF5 is a homologue of microtubule-associated protein MAP1B that interacts with natural paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Although normally distributed throughout the cytosol, C19ORF5 specifically associates with microtubules stabilized by paclitaxel or RASSF1A. At sufficiently high concentrations, C19ORF5 causes mitochondrial aggregation and genome destruction (MAGD). The accumulation on hyperstabilized microtubules coupled to MAGD has been proposed to mediate tumor suppression by the taxoid drug family and RASSF1A. Here, we show that the C-terminus of C19ORF5 (C19ORF5C) interacts with mitochondria-associated DNA binding protein, LRPPRC, in liver cells. Like LRPPRC, C19ORF5 also binds DNA with an affinity and specificity sufficient to be of utility in DNA affinity chromatography to purify homogeneous recombinant C19ORF5C from bacterial extracts. Homogeneous C19ORF5 exhibited no intrinsic DNase activity. Deletion mutagenesis indicated that C19ORF5 selectively binds double stranded DNA through its microtubule binding domain. These results suggest C19ORF5 as a DNA binding protein similar to microtubule-associated proteins tau and MAP2.

SUBMITTER: Liu L

PROVIDER: S-EPMC3225229 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein.

Liu Leyuan L Vo Amy A Liu Guoqin G McKeehan Wallace L WL

Biochemical and biophysical research communications 20050701 3

C19ORF5 is a homologue of microtubule-associated protein MAP1B that interacts with natural paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Although normally distributed throughout the cytosol, C19ORF5 specifically associates with microtubules stabilized by paclitaxel or RASSF1A. At sufficiently high concentrations, C19ORF5 causes mitochondrial aggregation and genome destruction (MAGD). The accumulation on hyperstabilized microtubules coupled to MAGD has been propos ...[more]

PMID: 15907802

Similar Datasets

Project description:The Ras Association Domain Family Member 1 (RASSF1) is one of the most frequently reported methylation-inactivated tumor suppressor genes in primary pancreatic ductal adenocarcinomas (PDAC). Limited information is still available about the impact of RASSF1 gene silencing on the expression of its different isoforms in neoplastic cells.A series of 96 primary PDAC, with known clinico-pathological parameters, was tested for RASSF1 methylation status by methylation-specific PCR, RASSF1 locus copy number alterations by fluorescence in situ hybridization, and Rassf1a protein expression by immunohistochemistry. A further series of 14 xenografted primary PDAC and 8 PDAC-derived cell lines were tested to obtain a detailed methylation mapping of CpG islands A and C of the RASSF1 locus by pyrosequencing and to evaluate the expression of Rassf1 variants by qRT-PCR.Methylation of CpG island A of the RASSF1 gene was observed in 35% of the tumors and allelic loss of RASSF1 locus was seen in 30 disomic and in 20 polysomic cases (52%). Rassf1a immunohistochemical expression was downregulated in half of primary PDAC, and this downregulation was neither correlated with methylation of RASSF1 promoter nor with RASSF1 copy number alterations. RASSF1 status did not influence patients' prognosis. The expression of the seven RASSF1 isoforms in xenografts and cell lines showed that RASSF1A, RASSF1B, and RASSF1C isoforms were present in all xenografts and cell lines, whereas RASSF1D, RASSF1E, and RASSF1F isoforms were variably expressed among samples. RASSF1G was never expressed in either xenografts or cell lines. The variable expression of RASSF1 isoforms in PDAC xenografts and cell lines was not dependent on RASSF1 methylation status of CpG islands A and C.RASSF1 alterations occurring in PDAC mainly consist in variations of expression of the different isoforms. Different genetic mechanisms seem to contribute to RASSF1 deregulation in this setting, but RASSF1 methylation does not seem to substantially affect RASSF1 isoforms expression.

Dataset Information

Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein.

Publications

Putative tumor suppressor RASSF1 interactive protein and cell death inducer C19ORF5 is a DNA binding protein.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets