Abstract
Previous work had identified a corepressor, NAB1, which represses transcriptional activation mediated by NGFI-A (also known as Egr-1, zif268, and Krox24) and Krox20. These zinc finger transcription factors are encoded by immediate-early genes and have been implicated in a wide variety of proliferative and differentiative processes. We have isolated and characterized another corepressor, NAB2, which is highly related to NAB1 within two discrete domains. The first conserved domain of NAB2 mediates an interaction with the R1 domain of NGFI-A. NAB2 represses the activity of both NGFI-A and Krox20, and its expression is regulated by some of the same stimuli that induce NGFI-A expression, including serum stimulation of fibroblasts and nerve growth factor stimulation of PC12 cells. The human NAB2 gene has been localized to chromosome 12ql3.3-14.1, a region that is rearranged in several solid tumors, lipomas, uterine leiomyomata, and liposarcomas. Sequencing of the Caenorhabditis elegans genome has identified a gene that bears high homology to both NAB1 and NAB2, suggesting that NAB molecules fulfill an evolutionarily conserved role.
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- Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
- Bairoch A. The PROSITE dictionary of sites and patterns in proteins, its current status. Nucleic Acids Res. 1993 Jul 1;21(13):3097–3103. doi: 10.1093/nar/21.13.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brewer C. B. Cytomegalovirus plasmid vectors for permanent lines of polarized epithelial cells. Methods Cell Biol. 1994;43(Pt A):233–245. doi: 10.1016/s0091-679x(08)60606-8. [DOI] [PubMed] [Google Scholar]
- Bullerdiek J., Hutter K. J., Brandt G., Weinberg M., Belge G., Bartnitzke S. Cytogenetic investigations on a cell line derived from a carcinoma arising in a salivary gland pleomorphic adenoma. Cancer Genet Cytogenet. 1990 Feb;44(2):253–262. doi: 10.1016/0165-4608(90)90054-e. [DOI] [PubMed] [Google Scholar]
- Bérubé N. G., Speevak M. D., Chevrette M. Suppression of tumorigenicity of human prostate cancer cells by introduction of human chromosome del(12)(q13). Cancer Res. 1994 Jun 15;54(12):3077–3081. [PubMed] [Google Scholar]
- Cao X. M., Koski R. A., Gashler A., McKiernan M., Morris C. F., Gaffney R., Hay R. V., Sukhatme V. P. Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals. Mol Cell Biol. 1990 May;10(5):1931–1939. doi: 10.1128/mcb.10.5.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Changelian P. S., Feng P., King T. C., Milbrandt J. Structure of the NGFI-A gene and detection of upstream sequences responsible for its transcriptional induction by nerve growth factor. Proc Natl Acad Sci U S A. 1989 Jan;86(1):377–381. doi: 10.1073/pnas.86.1.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
- Christy B. A., Lau L. F., Nathans D. A gene activated in mouse 3T3 cells by serum growth factors encodes a protein with "zinc finger" sequences. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7857–7861. doi: 10.1073/pnas.85.21.7857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Day M. L., Fahrner T. J., Aykent S., Milbrandt J. The zinc finger protein NGFI-A exists in both nuclear and cytoplasmic forms in nerve growth factor-stimulated PC12 cells. J Biol Chem. 1990 Sep 5;265(25):15253–15260. [PubMed] [Google Scholar]
- Durfee T., Becherer K., Chen P. L., Yeh S. H., Yang Y., Kilburn A. E., Lee W. H., Elledge S. J. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. doi: 10.1101/gad.7.4.555. [DOI] [PubMed] [Google Scholar]
- Fejzo M. S., Yoon S. J., Montgomery K. T., Rein M. S., Weremowicz S., Krauter K. S., Dorman T. E., Fletcher J. A., Mao J. I., Moir D. T. Identification of a YAC spanning the translocation breakpoints in uterine leiomyomata, pulmonary chondroid hamartoma, and lipoma: physical mapping of the 12q14-q15 breakpoint region in uterine leiomyomata. Genomics. 1995 Mar 20;26(2):265–271. doi: 10.1016/0888-7543(95)80210-d. [DOI] [PubMed] [Google Scholar]
- Fields S., Sternglanz R. The two-hybrid system: an assay for protein-protein interactions. Trends Genet. 1994 Aug;10(8):286–292. doi: 10.1016/0168-9525(90)90012-u. [DOI] [PubMed] [Google Scholar]
- Frohman M. A. Rapid amplification of complementary DNA ends for generation of full-length complementary DNAs: thermal RACE. Methods Enzymol. 1993;218:340–356. doi: 10.1016/0076-6879(93)18026-9. [DOI] [PubMed] [Google Scholar]
- Gashler A. L., Swaminathan S., Sukhatme V. P. A novel repression module, an extensive activation domain, and a bipartite nuclear localization signal defined in the immediate-early transcription factor Egr-1. Mol Cell Biol. 1993 Aug;13(8):4556–4571. doi: 10.1128/mcb.13.8.4556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gashler A., Sukhatme V. P. Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Nucleic Acid Res Mol Biol. 1995;50:191–224. doi: 10.1016/s0079-6603(08)60815-6. [DOI] [PubMed] [Google Scholar]
- Hörlein A. J., När A. M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C. K. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5;377(6548):397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
- Krishnaraju K., Nguyen H. Q., Liebermann D. A., Hoffman B. The zinc finger transcription factor Egr-1 potentiates macrophage differentiation of hematopoietic cells. Mol Cell Biol. 1995 Oct;15(10):5499–5507. doi: 10.1128/mcb.15.10.5499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lau L. F., Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1182–1186. doi: 10.1073/pnas.84.5.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lemaire P., Revelant O., Bravo R., Charnay P. Two mouse genes encoding potential transcription factors with identical DNA-binding domains are activated by growth factors in cultured cells. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4691–4695. doi: 10.1073/pnas.85.13.4691. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matheny C., Day M. L., Milbrandt J. The nuclear localization signal of NGFI-A is located within the zinc finger DNA binding domain. J Biol Chem. 1994 Mar 18;269(11):8176–8181. [PubMed] [Google Scholar]
- Milbrandt J. A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science. 1987 Nov 6;238(4828):797–799. doi: 10.1126/science.3672127. [DOI] [PubMed] [Google Scholar]
- Milbrandt J. Nerve growth factor rapidly induces c-fos mRNA in PC12 rat pheochromocytoma cells. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4789–4793. doi: 10.1073/pnas.83.13.4789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Molnar G., Crozat A., Pardee A. B. The immediate-early gene Egr-1 regulates the activity of the thymidine kinase promoter at the G0-to-G1 transition of the cell cycle. Mol Cell Biol. 1994 Aug;14(8):5242–5248. doi: 10.1128/mcb.14.8.5242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muthukkumar S., Nair P., Sells S. F., Maddiwar N. G., Jacob R. J., Rangnekar V. M. Role of EGR-1 in thapsigargin-inducible apoptosis in the melanoma cell line A375-C6. Mol Cell Biol. 1995 Nov;15(11):6262–6272. doi: 10.1128/mcb.15.11.6262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paulsen R. E., Weaver C. A., Fahrner T. J., Milbrandt J. Domains regulating transcriptional activity of the inducible orphan receptor NGFI-B. J Biol Chem. 1992 Aug 15;267(23):16491–16496. [PubMed] [Google Scholar]
- Popescu N. C., Amsbaugh S. C., DiPaolo J. A. Human papillomavirus type 18 DNA is integrated at a single chromosome site in cervical carcinoma cell line SW756. J Virol. 1987 May;61(5):1682–1685. doi: 10.1128/jvi.61.5.1682-1685.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Popescu N., Zimonjic D., Hatch C., Bonner W. Chromosomal mapping of the human histone gene H2AZ to 4q24 by fluorescence in situ hybridization. Genomics. 1994 Mar 15;20(2):333–335. doi: 10.1006/geno.1994.1182. [DOI] [PubMed] [Google Scholar]
- Reifenberger G., Reifenberger J., Ichimura K., Collins V. P. Amplification at 12q13-14 in human malignant gliomas is frequently accompanied by loss of heterozygosity at loci proximal and distal to the amplification site. Cancer Res. 1995 Feb 15;55(4):731–734. [PubMed] [Google Scholar]
- Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
- Russo M. W., Matheny C., Milbrandt J. Transcriptional activity of the zinc finger protein NGFI-A is influenced by its interaction with a cellular factor. Mol Cell Biol. 1993 Nov;13(11):6858–6865. doi: 10.1128/mcb.13.11.6858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Russo M. W., Sevetson B. R., Milbrandt J. Identification of NAB1, a repressor of NGFI-A- and Krox20-mediated transcription. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6873–6877. doi: 10.1073/pnas.92.15.6873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider-Maunoury S., Topilko P., Seitandou T., Levi G., Cohen-Tannoudji M., Pournin S., Babinet C., Charnay P. Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain. Cell. 1993 Dec 17;75(6):1199–1214. doi: 10.1016/0092-8674(93)90329-o. [DOI] [PubMed] [Google Scholar]
- Sells S. F., Muthukumar S., Sukhatme V. P., Crist S. A., Rangnekar V. M. The zinc finger transcription factor EGR-1 impedes interleukin-1-inducible tumor growth arrest. Mol Cell Biol. 1995 Feb;15(2):682–692. doi: 10.1128/mcb.15.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seyfert V. L., McMahon S. B., Glenn W. D., Yellen A. J., Sukhatme V. P., Cao X. M., Monroe J. G. Methylation of an immediate-early inducible gene as a mechanism for B cell tolerance induction. Science. 1990 Nov 9;250(4982):797–800. doi: 10.1126/science.2237429. [DOI] [PubMed] [Google Scholar]
- Seyfert V. L., Sukhatme V. P., Monroe J. G. Differential expression of a zinc finger-encoding gene in response to positive versus negative signaling through receptor immunoglobulin in murine B lymphocytes. Mol Cell Biol. 1989 May;9(5):2083–2088. doi: 10.1128/mcb.9.5.2083. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Solomon E., Borrow J., Goddard A. D. Chromosome aberrations and cancer. Science. 1991 Nov 22;254(5035):1153–1160. doi: 10.1126/science.1957167. [DOI] [PubMed] [Google Scholar]
- Sukhatme V. P., Cao X. M., Chang L. C., Tsai-Morris C. H., Stamenkovich D., Ferreira P. C., Cohen D. R., Edwards S. A., Shows T. B., Curran T. A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell. 1988 Apr 8;53(1):37–43. doi: 10.1016/0092-8674(88)90485-0. [DOI] [PubMed] [Google Scholar]
- Suva L. J., Ernst M., Rodan G. A. Retinoic acid increases zif268 early gene expression in rat preosteoblastic cells. Mol Cell Biol. 1991 May;11(5):2503–2510. doi: 10.1128/mcb.11.5.2503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Topilko P., Schneider-Maunoury S., Levi G., Baron-Van Evercooren A., Chennoufi A. B., Seitanidou T., Babinet C., Charnay P. Krox-20 controls myelination in the peripheral nervous system. Nature. 1994 Oct 27;371(6500):796–799. doi: 10.1038/371796a0. [DOI] [PubMed] [Google Scholar]
- Treitel M. A., Carlson M. Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3132–3136. doi: 10.1073/pnas.92.8.3132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tzamarias D., Struhl K. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature. 1994 Jun 30;369(6483):758–761. doi: 10.1038/369758a0. [DOI] [PubMed] [Google Scholar]
- Van de Ven W. J., Schoenmakers E. F., Wanschura S., Kazmierczak B., Kools P. F., Geurts J. M., Bartnitzke S., Van den Berghe H., Bullerdiek J. Molecular characterization of MAR, a multiple aberration region on human chromosome segment 12q13-q15 implicated in various solid tumors. Genes Chromosomes Cancer. 1995 Apr;12(4):296–303. doi: 10.1002/gcc.2870120410. [DOI] [PubMed] [Google Scholar]
- Varnum B. C., Lim R. W., Kujubu D. A., Luner S. J., Kaufman S. E., Greenberger J. S., Gasson J. C., Herschman H. R. Granulocyte-macrophage colony-stimulating factor and tetradecanoyl phorbol acetate induce a distinct, restricted subset of primary-response TIS genes in both proliferating and terminally differentiated myeloid cells. Mol Cell Biol. 1989 Aug;9(8):3580–3583. doi: 10.1128/mcb.9.8.3580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waterston R., Sulston J. The genome of Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10836–10840. doi: 10.1073/pnas.92.24.10836. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watson M. A., Milbrandt J. Expression of the nerve growth factor-regulated NGFI-A and NGFI-B genes in the developing rat. Development. 1990 Sep;110(1):173–183. doi: 10.1242/dev.110.1.173. [DOI] [PubMed] [Google Scholar]
- Weinberg R. A. The retinoblastoma protein and cell cycle control. Cell. 1995 May 5;81(3):323–330. doi: 10.1016/0092-8674(95)90385-2. [DOI] [PubMed] [Google Scholar]
- Weintraub S. J., Chow K. N., Luo R. X., Zhang S. H., He S., Dean D. C. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature. 1995 Jun 29;375(6534):812–815. doi: 10.1038/375812a0. [DOI] [PubMed] [Google Scholar]
- Xu J., Wang N. Identification of chromosomal structural alterations in human ovarian carcinoma cells using combined GTG-banding and repetitive fluorescence in situ hybridization (FISH). Cancer Genet Cytogenet. 1994 May;74(1):1–7. doi: 10.1016/0165-4608(94)90020-5. [DOI] [PubMed] [Google Scholar]
- Zimonjic D. B., Popescu N. C., Matsui T., Ito M., Chihara K. Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to chromosome 11p15.5-->p15.4 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;65(3):184–185. doi: 10.1159/000133628. [DOI] [PubMed] [Google Scholar]
- Zimonjic D. B., Rezanka L., DiPaolo J. A., Popescu N. C. Refined localization of the erbB-3 proto-oncogene by direct visualization of FISH signals on LUT-inverted and contrast-enhanced digital images of DAPI-banded chromosomes. Cancer Genet Cytogenet. 1995 Apr;80(2):100–102. doi: 10.1016/0165-4608(94)00161-4. [DOI] [PubMed] [Google Scholar]