Co-Authors:
Zamostiano, R., Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Pinhasov, A., Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Gelber, E., Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Steingart, R.A., Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Seroussi, E., Institute of Animal Science, Volcani Center, Bet-Dagan 60260, Israel
Giladi, E., Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Bassan, M., Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Wollman, Y., Department of Nephrology, Tel Aviv Medical Center, Tel Aviv 64239, Israel
Eyre, H.J., Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children Hospital, Adelaide, SA 6006, Australia
Mulley, J.C., Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children Hospital, Adelaide, SA 6006, Australia, Department of Genetics, University of Adelaide, Adelaide, SA 6006, Australia
Brenneman, D.E., Section on Developmental and Molecular Pharmacology, NICHD, National Institutes of Health, Bethesda, MD 20892, United States
Gozes, I., Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Abstract:
We have recently cloned the mouse activity-dependent neuroprotective protein (ADNP). Here, we disclose the cloning of human ADNP (hADNP) from a fetal brain cDNA library. Comparative sequence analysis of these two ADNP orthologs indicated 99% identity at the mRNA level. Several single nucleotide polymorphic sites were noticed. The deduced protein structure contained nine zinc fingers, a proline-rich region, a nuclear bipartite localization signal, and a homeobox domain profile, suggesting a transcription factor function. Further comparative analysis identified an ADNP paralog (33% identity and 46% similarity), indicating that these genes belong to a novel protein family with a nine-zinc finger motif followed by a homeobox domain. The hADNP gene structure spans ∼40 kilobases and includes five exons and four introns with alternative splicing of an untranslated second exon. The hADNP gene was mapped to chromosome 29q12-13.2, a region associated with aggressive tumor growth, frequently amplified in many neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers, hADNP mRNA is abundantly expressed in distinct normal tissues, and high expression levels were encountered in malignant cells. Down-regulation of ADNP by antisense oligodeoxynucleotides up-regulated the tumor suppressor p53 and reduced file viability of intestinal cancer cells by 90%. Thus, ADNP is implicated in maintaining cell survival, perhaps through modulation of p53.
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