Rabbit Anti-Human YWHAQ (Phospho Ser232) Polyclonal antibody

We have recently isolated a 2.2-kb cDNA clone (1C5) from a human spinal cord cDNA library with partial identity to the 14-3-3 protein mRNA encoding the a protein (YWHAQ). 14-3-3 protein transcripts are highly expressed in large projection neurones of the hippocampus, cerebellum, and spinal cord and have been found to be significantly up-regulated in rat motor neurones following hypoglossal nerve axotomy. In this study we investigated whether the 1C5 transcript (YWHAQ) isolated from spinal cord was involved in amyotrophic lateral sclerosis (ALS). We found a significant up-regulation of 1C5 (YWHAQ) in lumbar spinal cord from patients with sporadic ALS compared with controls, with the highest levels of expression being found in individuals with predominant lower motor neurone involvement. A 6-bp tandem repeat in the 5'-untranslated region of the gene was found to be polymorphic, but no significant association with disease was found following genomic analysis of this region. The localisation of 1C5 (YWHAQ) to chromosome 2 was determined and coincides with that reported for clone HS1 (EMBL accession no. X57347), These results show the marked up-regulation of the 14-3-3 isoform (YWHAQ) in ALS spinal cord and indicate the involvement of a potential 14-3-3-mediated survival pathway in the pathogenesis of ALS.

The p53 regulatory network responds to cellular stresses by initiating processes such as cell cycle arrest and apoptosis. These responses inhibit cellular transformation and mediate the response to many forms of cancer therapies. Functional variants in the genes comprising this network could help identify individuals at greater risk for cancer and patients with poorer responses to therapies, but few such variants have been identified as yet. We use the NCI60 human tumor cell line anticancer drug screen in a scan of single nucleotide polymorphisms (SNP) in 142 p53 stress response genes and identify 7 SNPs that exhibit allelic differences in cellular responses to a large panel of cytotoxic chemotherapeutic agents. The greatest differences are observed for SNPs in 14-3-3 tau (YWHAQ; rs6734469, P = 5.6 x 10(-47)) and CD44 (rs187115, P = 8.1 x 10(-24)). In soft-tissue sarcoma patients, we find that the alleles of these SNPs that associate with weaker growth responses to chemotherapeutics associate with poorer overall survival (up to 2.89 relative risk, P = 0.011) and an earlier age of diagnosis (up to 10.7 years earlier, P = 0.002). Our findings define genetic markers in 14-3-3 tau and CD44 that might improve the treatment and prognosis of soft-tissue sarcomas. Cancer Res; 70(1); 172-80. (C)2010 AACR.