Infection with SIVmac251 in some rhesus monkeys (Macaca mulatta) leads to B-cell non-Hodgkin's lymphomas (B-NHL) clinically similar to that of HIV-infected AIDS patients. To further characterize the SIV-associated B-NHL we have generated genetic profiles of malignant cells by subtractive hybridization and Northern blot analysis. We have analyzed 21 clones of a subtracted cDNA library corresponding to overexpressed genes in diffuse large B-cell (DLBCL) SIV-associated monkey lymphoma. Eight of these clones represent a sequence homologous to an abundant transcript from KG-1 cells originally established from a human myelogenous leukemia. The protein encoded has a 60% similarity to a hypothetical glycine-rich transmembrane signal protein of Caenorhabditis elegans and 25% similarity to the ret finger protein. The other cDNA clones contained sequences of the serum amyloid A gene (SAA), the alpha1-acid glycoprotein gene (AGP), the ribosomal protein S3a (RPS3a) and L8 (RPL8) genes, the interferon-inducible gene (INF-ind), the metastasin gene (mts1), and the NADH dehydrogenase I gene (ND-I). The remaining cDNA clones consisted of yet unknown sequences. In addition, we detected an up-regulation of the cytochrome c oxidase II gene (COX-II), the ND-IV gene, and the SET oncogene by Northern blot hybridization in three SIV-associated NHLs of different histomorphological classification. All these genes have not previously been found to be overexpressed in B-NHL.
Humanin (HN), a 24-amino acid peptide encoded by the mitochondrial 16S rRNA gene, was discovered by screening a cDNA library from the occipital cortex of a patient with Alzheimer's disease (AD) for a protection factor against AD-relevant insults. Earlier, using the yeast two-hybrid system, we have identified the M-phase phosphoprotein 8 (MPP8) as a binding partner for HN. In the present work, we further confirmed interaction of HN with MPP8 in co-immunoprecipitation experiments and localized an MPP8-binding site in the region between 5 and 12 aa. of HN. We have also shown that an MPP8 fragment (residues 431-560) is sufficient to bind HN. Further studies on functional consequences of the interaction between the potential oncopetide and the oncoprotein may elucidate some aspects of the molecular mechanisms of carcinogenesis.
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