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Type: Journal article
Title: Cloning and characterization of the human activity-dependent neuroprotective protein
Author: Zamostiano, R.
Pinhasov, A.
Gelber, E.
Steingart, R.
Seroussi, E.
Giladi, E.
Bassan, M.
Wollman, Y.
Eyre, H.
Mulley, J.
Brenneman, D.
Gozes, I.
Citation: Journal of Biological Chemistry, 2001; 276(1):708-714
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2001
ISSN: 0021-9258
Statement of
Rachel Zamostiano, Albert Pinhasov, Edgar Gelber, Ruth A. Steingart, Eyal Seroussi, Eliezer Giladi, Merav Bassan, Yoram Wollman, Helen J. Eyre, John C. Mulley, Douglas E. Brenneman and Illana Gozes
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 90% 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 approximately 40 kilobases and includes five exons and four introns with alternative splicing of an untranslated second exon. The hADNP gene was mapped to chromosome 20q12-13.2, 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 the viability of intestinal cancer cells by 90%. Thus, ADNP is implicated in maintaining cell survival, perhaps through modulation of p53.
Keywords: Tumor Cells, Cultured
Chromosomes, Human, Pair 20
Homeodomain Proteins
Neoplasm Proteins
Nerve Tissue Proteins
Oligonucleotides, Antisense
RNA, Messenger
Blotting, Western
Physical Chromosome Mapping
Cloning, Molecular
Gene Expression Profiling
Sequence Alignment
Cell Division
Alternative Splicing
Amino Acid Sequence
Base Sequence
Conserved Sequence
Zinc Fingers
Polymorphism, Single Nucleotide
Molecular Sequence Data
Tumor Suppressor Protein p53
DOI: 10.1074/jbc.M007416200
Appears in Collections:Aurora harvest 2
Molecular and Biomedical Science publications

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