Abstract
We isolated several related but distinct cDNA clones encoding novel structure proteins (NSP) when screening a cDNA library. Analysis revealed that these cDNAs and several similar ESTs in the public databases are derived from a single gene of 17 exons that span a minimum of 227-kb region. This gene is located at chromosome 17p11.2, a region frequently amplified in human gliomas and osteosarcomas, and involved in Birt–Hogg–Dube syndrome, a tumor-prone syndrome. The major coding sequences shared by all isolated transcripts are predicted to encode SMC (structural maintenance of chromosome)/SbcC ATPase motifs and coiled-coil domains commonly seen in motor or structure proteins. Two 5′-end and two 3′-end variants (type 5α/β and 3α/β, respectively) were identified, making a total of four possible transcripts. Both 5α and 5β variants were detected in human testis mRNA, but only type 5α was detectable in RNA samples extracted from HeLa cells. The unique carboxyl-terminus of 3β contains a Ca2+-dependent actin-binding domain. Immunohistochemistry studies revealed that NSPs were mostly localized to nuclei. Northern blot analysis demonstrated two major bands and the expression levels are tremendously high in testis while barely detectable in other normal tissues examined. Interestingly, NSP5α3α is highly expressed in some tumor cell lines. These results suggest that NSPs represent a new family of structure proteins with a possible role in nuclear dynamics during cell division, and that NSP5α3α may serve as a tumor marker.
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Acknowledgements
This work was initiated in Dr Giordano's laboratory in Temple University as part of the thesis research of NS and supported by various grants (NIH and Searro Health Research Organization www.shro.org) to AG Late work of this project was partly supported by fund from Cardeza Foundation and Howard Temin award from NIH/NCI to NS. NS acknowledges the support from Dr J Caro and Dr S Mckenzie. We thank Dr HHQ Heng for his expertise in FISH analysis and Mr Likens for his professional assistance in preparation of illustrations.
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Sang, N., Fath, D. & Giordano, A. A gene highly expressed in tumor cells encodes novel structure proteins. Oncogene 23, 9438–9446 (2004). https://doi.org/10.1038/sj.onc.1207988
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DOI: https://doi.org/10.1038/sj.onc.1207988
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