LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis

Sutherland, Leslie C.; Edwards, Sandra E.; Cable, Hazel C.; Poirier, Guy G.; Miller, Barbara A.; Cooper, Christopher S.; Williams, Gwyn T.

doi:10.1038/sj.onc.1203720

Cited by 50 publications

(98 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The key advantage of this strategy is that it identifies those genes that play a causal role in the cell death process, and distinguishes this crucial group of genes from those that are differentially expressed but do not affect the cell death/survival decision (Sutherland et al, 2000;Mourtada-Maarabouni et al, 2002, 2003a, b, 2004, 2005Williams et al, 2006; reviewed in Williams and Farzaneh, 2004).…”

Section: Introductionmentioning

confidence: 99%

GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer

et al. 2008

View full text Add to dashboard Cite

Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Ectopic expression of H37 also suppresses growth of HT 1080 fibrosarcoma cells [15]. Alternatively-spliced transcripts from the H37 locus and antisense fragments also serve as apoptotic regulators in hematopoetic cells [16][17][18][19][20]. Most significantly, the H37/RBM5 gene was included in the 17 common gene signature associated with metastasis (one of the nine genes down-regulated in metastases) identified in multiple solid tumour types [21].…”

Section: Introductionmentioning

confidence: 99%

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

Koegel

Phan

et al. 2007

Lung Cancer

View full text Add to dashboard Cite

SummaryAllele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour vs. adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected, instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC) whereas homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals. Keywords lung cancer; H37/RBM5/Luca15; single nucleotide polymorphism; 3p21.3; tumour suppressor gene; linkage disequilibrium; loss of heterozygosity

show abstract

“…A 326-base-pair (bp) fragment of cDNA from the RBM5 locus was identified as a suppressor of Fas-mediated apoptosis in a cDNA screen (Sutherland et al 2000). It was soon realized that this encoded an inhibitory RNA complementary to the 39 untranslated region (UTR) of the RBM5 mRNA, and that full-length, sense-oriented RBM5 actually potentiates apoptosis initiated by Fas (Rintala-Maki and Sutherland 2004).…”

Section: Rna-binding Motif 5 (Rbm5)mentioning

confidence: 99%

Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged

David

Manley²

2010

Genes Dev.

727

667

View full text Add to dashboard Cite

Alternative splicing of mRNA precursors is a nearly ubiquitous and extremely flexible point of gene control in humans. It provides cells with the opportunity to create protein isoforms of differing, even opposing, functions from a single gene. Cancer cells often take advantage of this flexibility to produce proteins that promote growth and survival. Many of the isoforms produced in this manner are developmentally regulated and are preferentially re-expressed in tumors. Emerging insights into this process indicate that pathways that are frequently deregulated in cancer often play important roles in promoting aberrant splicing, which in turn contributes to all aspects of tumor biology.

show abstract

LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis

Cited by 50 publications

References 38 publications

GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer

GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged

Contact Info

Product

Resources

About