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 NAB2gene.[1][2][3]
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]
↑Kirsch KH, Korradi Y, Johnson JP (Jul 1996). "Mader: a novel nuclear protein over expressed in human melanomas". Oncogene. 12 (5): 963–71. PMID8649813.
↑Kabbinavar, F. F.; Hambleton, J; Mass, R. D.; Hurwitz, H. I.; Bergsland, E; Sarkar, S (2005). "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. doi:10.1200/JCO.2005.00.232. PMID15867200.
Further reading
Svaren J, Apel ED, Simburger KS, et al. (1997). "The Nab2 and Stat6 genes share a common transcription termination region". Genomics. 41 (1): 33–9. doi:10.1006/geno.1997.4609. PMID9126479.
Abdulkadir SA, Qu Z, Garabedian E, et al. (2001). "Impaired prostate tumorigenesis in Egr1-deficient mice". Nat. Med. 7 (1): 101–7. doi:10.1038/83231. PMID11135623.
Abdulkadir SA, Carbone JM, Naughton CK, et al. (2001). "Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma". Hum. Pathol. 32 (9): 935–9. doi:10.1053/hupa.2001.27102. PMID11567222.
Venken K, Di Maria E, Bellone E, et al. (2003). "Search for mutations in the EGR2 corepressor proteins, NAB1 and NAB2, in human peripheral neuropathies". Neurogenetics. 4 (1): 37–41. doi:10.1007/s10048-001-0124-2. PMID12030330.
Lucerna M, Mechtcheriakova D, Kadl A, et al. (2003). "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. doi:10.1074/jbc.M204937200. PMID12427750.
Kumbrink J, Gerlinger M, Johnson JP (2005). "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. doi:10.1074/jbc.M511079200. PMID16260776.
Srinivasan R, Mager GM, Ward RM, et al. (2006). "NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex". J. Biol. Chem. 281 (22): 15129–37. doi:10.1074/jbc.M600775200. PMID16574654.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.
