NAB2 explained

NGFI-A-binding protein 2 also known as EGR-1-binding protein 2 or melanoma-associated delayed early response protein (MADER) is a protein that in humans is encoded by the NAB2 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the family of NGFI-A binding (NAB) proteins, which function in the nucleus to repress or activate transcription induced by some members of the EGR (early growth response) family of transactivators. NAB proteins can homo- or hetero-multimerize with other EGR or NAB proteins through a conserved N-terminal domain, and repress transcription through two partially redundant C-terminal domains. Transcriptional repression by the encoded protein is mediated in part by interactions with the nucleosome remodeling and deactylase (NuRD) complex. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.^[3]

Pathology

Recurrent somatic fusions of the two genes, NGFI-A–binding protein 2 (NAB2) and STAT6, located at chromosomal region 12q13, have been identified in solitary fibrous tumors.^[4]

Further reading

• Svaren J, Apel ED, Simburger KS, etal . The Nab2 and Stat6 genes share a common transcription termination region. . Genomics . 41 . 1 . 33–9 . 1997 . 9126479 . 10.1006/geno.1997.4609 .
• Qu Z, Wolfraim LA, Svaren J, etal . The transcriptional corepressor NAB2 inhibits NGF-induced differentiation of PC12 cells. . J. Cell Biol. . 142 . 4 . 1075–82 . 1998 . 9722618 . 10.1083/jcb.142.4.1075 . 2132876 .
• Svaren J, Sevetson BR, Golda T, etal . Novel mutants of NAB corepressors enhance activation by Egr transactivators. . EMBO J. . 17 . 20 . 6010–9 . 1998 . 9774344 . 10.1093/emboj/17.20.6010 . 1170927 .
• Abdulkadir SA, Qu Z, Garabedian E, etal . Impaired prostate tumorigenesis in Egr1-deficient mice. . Nat. Med. . 7 . 1 . 101–7 . 2001 . 11135623 . 10.1038/83231 . 7191051 .
• Abdulkadir SA, Carbone JM, Naughton CK, etal . Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma. . Hum. Pathol. . 32 . 9 . 935–9 . 2001 . 11567222 . 10.1053/hupa.2001.27102 .
• Venken K, Di Maria E, Bellone E, etal . Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies. . Neurogenetics . 4 . 1 . 37–41 . 2003 . 12030330 . 10.1007/s10048-001-0124-2 . 1928229 .
• Lucerna M, Mechtcheriakova D, Kadl A, etal . NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells. . J. Biol. Chem. . 278 . 13 . 11433–40 . 2003 . 12427750 . 10.1074/jbc.M204937200 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Kumbrink J, Gerlinger M, Johnson JP . Egr-1 induces the expression of its corepressor nab2 by activation of the nab2 promoter thereby establishing a negative feedback loop. . J. Biol. Chem. . 280 . 52 . 42785–93 . 2005 . 16260776 . 10.1074/jbc.M511079200 . free .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 .
• Srinivasan R, Mager GM, Ward RM, etal . NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex. . J. Biol. Chem. . 281 . 22 . 15129–37 . 2006 . 16574654 . 10.1074/jbc.M600775200 . free .
• Olsen JV, Blagoev B, Gnad F, etal . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .

Notes and References

1. Svaren J, Sevetson BR, Apel ED, Zimonjic DB, Popescu NC, Milbrandt J . NAB2, a corepressor of NGFI-A (Egr-1) and Krox20, is induced by proliferative and differentiative stimuli . Mol Cell Biol . 16 . 7 . 3545–53 . Aug 1996 . 8668170 . 231349 . 10.1128/MCB.16.7.3545.
2. Kirsch KH, Korradi Y, Johnson JP . Mader: a novel nuclear protein over expressed in human melanomas . Oncogene . 12 . 5 . 963–71 . Jul 1996 . 8649813 .
3. Web site: Entrez Gene: NAB2 NGFI-A binding protein 2 (EGR1 binding protein 2).
4. 15867200. 2005. Kabbinavar. F. F.. Combined analysis of efficacy: The addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. Journal of Clinical Oncology. 23. 16. 3706–12. Hambleton. J. Mass. R. D.. Hurwitz. H. I.. Bergsland. E. Sarkar. S. 10.1200/JCO.2005.00.232. free.