Cloning and Characterization of the Human Activity-dependent Neuroprotective Protein
Open accessAbstract
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.
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TP53 expression was significantly increased in the patients.
“Expression levels of TP53, reported upregulated in HT29 cells incubated with ADNP antioligodeoxynucleotide32, were significantly increased (Supplementary Fig. 3g)”
From A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP (2014) · cites this paper as [32]
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References 39 · Cited by 251
Research works printed but not linked: 5
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- Authors
- Zamostiano, R., Pinhasov, A., Gelber, E., Steingart, R. A., Seroussi, E., Giladi, E., Bassan, M., Wollman, Y., Eyre, H. J., Mulley, J. C., Brenneman, D. E., & Gozes, I.
- Affiliations
- Tel Aviv University (IL)
- Agricultural Research Organization (IL)
- Tel Aviv Sourasky Medical Center (IL)
- Women's and Children's Hospital (AU)
- National Institutes of Health (US)
- Corresponding author
- Gozes, Illana
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 276
- Issue
- 1
- Pages
- 708-714
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2114112734
- Cited by
- 251
- References
- 39
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 25 · 2023: 14 · 2022: 13 · 2021: 13 · 2020: 18 · 2019: 10 · 2018: 11 · 2017: 12 · 2016: 11 · 2015: 9 · 2014: 8 · 2013: 4 · 2012: 6
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- United States-Israel Binational Science Foundation
- Israel Science Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- ADNP, zinc finger, homeodomain, transcription factors, alternative splicing, antisense oligodeoxynucleotides, p53, tumor suppressor, intestinal cancer
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Division, Chromosomes, Human, Pair 20, Cloning, Molecular, Exons, Humans, Introns, Molecular Sequence Data, Neoplasm Proteins, Nerve Tissue Proteins, RNA, Messenger, Tumor Cells, Cultured, Blotting, Western, Tumor Suppressor Protein p53, Zinc Fingers, Oligonucleotides, Antisense, Sequence Alignment, Conserved Sequence, Alternative Splicing, Homeodomain Proteins, Physical Chromosome Mapping, Polymorphism, Single Nucleotide, Gene Expression Profiling
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