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Gene Review

SAFB  -  scaffold attachment factor B

Homo sapiens

Synonyms: HAP, HET, HSP27 ERE-TATA-binding protein, HSP27 estrogen response element-TATA box-binding protein, SAF-B, ...
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Disease relevance of SAFB


High impact information on SAFB


Chemical compound and disease context of SAFB

  • Since it has become clear that many steroid receptor cofactors play important roles in breast tumorigenesis, we investigated whether SAFB could also be involved in breast cancer [8].

Biological context of SAFB

  • LOH was detected at the marker D19S216, which colocalizes with the SAFB locus, in specimens from 29 (78.4%) of 37 informative patients [8].
  • SAFB1 and SAFB2 are mapped adjacent to each other on chromosome 19p13.3 and are arranged in a bidirectional divergent configuration (head to head), being separated by a short (<500 bp) GC-rich intergenic region that can function as a bidirectional promoter [1].
  • The association of SAFB1 and PPARgamma in vivo is further demonstrated by fluorescence resonance energy transfer (FRET) experiments in living cells [9].
  • The possibility that SAFB1 and SAFB2 are novel breast tumor suppressor genes, and how they might function in this role, are discussed [10].
  • Scaffold attachment factor B1 (SAFB1) and SAFB2 are large, multifunctional proteins that have been implicated in numerous cellular processes including chromatin organization, transcriptional regulation, RNA splicing, and stress response [10].

Anatomical context of SAFB

  • Coimmunoprecipitation experiments reveal that HET/SAF-B and ER associate in cell lines in the presence or absence of estradiol, but binding is increased by the antiestrogen tamoxifen [11].
  • Using novel mono-specific antisera, we found endogenous SAFB2 protein has a different spatial distribution from SAFB1 within the nucleus where it is found in much larger nuclear complexes (up to 670 kDa in size), and a distinct pattern of expression in adult human testis [12].
  • The HET clone is almost identical to a recently published scaffold attachment factor (SAF-B) cloned from a HeLa cell cDNA library [13].
  • We further demonstrate that enhanced green fluorescent protein (EGFP)- and DsRed-tagged ZO-2 and SAF-B fusion proteins partially co-localize in nuclei of transfected epithelial cells [14].
  • RESULTS: GHD subjects had a smaller thyroid volume (TV) than HET and CO [15].

Associations of SAFB with chemical compounds

  • Furthermore, our data showing that HET/SAF-B binds to ER particularly strongly in the presence of tamoxifen suggests that it may be important for the antagonist effect of tamoxifen [11].
  • Detailed kinetic studies showed that the addition of estrogen resulted in the concurrent release of SAFB1/2 and N-CoR from the promoter [16].
  • To confirm the identity of the HET clone, we expressed a partial HET clone as a glutathione S-transferase fusion protein, and showed binding to the hsp27 promoter fragment in gel-retardation assays [13].

Physical interactions of SAFB


Regulatory relationships of SAFB


Other interactions of SAFB

  • They are coexpressed in a number of tissues, but unlike SAFB1, which is exclusively nuclear, SAFB2 is found in the cytoplasm as well as the nucleus [1].
  • We asked the question whether SAFB1/2 and N-CoR could directly interact with each other, and whether this interaction results in altered repressive activities [16].
  • Using chromatin immunoprecipitation assays, we observed that SAFB1/2 and N-CoR were recruited to the pS2 promoter in the absence of estrogen, and this recruitment was enhanced in the presence of Tamoxifen [16].
  • Inhibition of oestrogen receptor activity by the co-repressor HET/SAF-B is relieved by blockade of histone deacetylase activity [18].
  • A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D [19].

Analytical, diagnostic and therapeutic context of SAFB


  1. SAFB2, a new scaffold attachment factor homolog and estrogen receptor corepressor. Townson, S.M., Dobrzycka, K.M., Lee, A.V., Air, M., Deng, W., Kang, K., Jiang, S., Kioka, N., Michaelis, K., Oesterreich, S. J. Biol. Chem. (2003) [Pubmed]
  2. Duodenal ulcer treated with Helicobacter pylori eradication: seven-year follow-up. Forbes, G.M., Glaser, M.E., Cullen, D.J., Warren, J.R., Christiansen, K.J., Marshall, B.J., Collins, B.J. Lancet (1994) [Pubmed]
  3. Progression of cervical intraepithelial neoplasia to cervical cancer: interactions of cytochrome P450 CYP2D6 EM and glutathione s-transferase GSTM1 null genotypes and cigarette smoking. Warwick, A.P., Redman, C.W., Jones, P.W., Fryer, A.A., Gilford, J., Alldersea, J., Strange, R.C. Br. J. Cancer (1994) [Pubmed]
  4. Protective effects of hochu-ekki-to, a Chinese traditional herbal medicine against murine cytomegalovirus infection. Hossain, M.S., Takimoto, H., Hamano, S., Yoshida, H., Ninomiya, T., Minamishima, Y., Kimura, G., Nomoto, K. Immunopharmacology (1999) [Pubmed]
  5. A comparative fine structure study on myofibroblasts from a cultured human and an in-situ rat tumor source. Reger, J.F., Dabbous, M.K. J. Submicrosc. Cytol. Pathol. (1988) [Pubmed]
  6. Software for analysis and manipulation of genetic linkage data. Weaver, R., Helms, C., Mishra, S.K., Donis-Keller, H. Am. J. Hum. Genet. (1992) [Pubmed]
  7. Disruption of Scaffold Attachment Factor B1 Leads to TBX2 Up-regulation, Lack of p19ARF Induction, Lack of Senescence, and Cell Immortalization. Dobrzycka, K.M., Kang, K., Jiang, S., Meyer, R., Rao, P.H., Lee, A.V., Oesterreich, S. Cancer Res. (2006) [Pubmed]
  8. High rates of loss of heterozygosity on chromosome 19p13 in human breast cancer. Oesterreich, S., Allredl, D.C., Mohsin, S.K., Zhang, Q., Wong, H., Lee, A.V., Osborne, C.K., O'Connell, P. Br. J. Cancer (2001) [Pubmed]
  9. Scaffold attachment factor B1 directly interacts with nuclear receptors in living cells and represses transcriptional activity. Debril, M.B., Dubuquoy, L., Feige, J.N., Wahli, W., Desvergne, B., Auwerx, J., Gelman, L. J. Mol. Endocrinol. (2005) [Pubmed]
  10. Scaffold attachment factors SAFB1 and SAFB2: Innocent bystanders or critical players in breast tumorigenesis? Oesterreich, S. J. Cell. Biochem. (2003) [Pubmed]
  11. Tamoxifen-bound estrogen receptor (ER) strongly interacts with the nuclear matrix protein HET/SAF-B, a novel inhibitor of ER-mediated transactivation. Oesterreich, S., Zhang, Q., Hopp, T., Fuqua, S.A., Michaelis, M., Zhao, H.H., Davie, J.R., Osborne, C.K., Lee, A.V. Mol. Endocrinol. (2000) [Pubmed]
  12. Alternative RNA splicing complexes containing the scaffold attachment factor SAFB2. Sergeant, K.A., Bourgeois, C.F., Dalgliesh, C., Venables, J.P., Stevenin, J., Elliott, D.J. J. Cell. Sci. (2007) [Pubmed]
  13. Novel nuclear matrix protein HET binds to and influences activity of the HSP27 promoter in human breast cancer cells. Oesterreich, S., Lee, A.V., Sullivan, T.M., Samuel, S.K., Davie, J.R., Fuqua, S.A. J. Cell. Biochem. (1997) [Pubmed]
  14. The tight junction protein ZO-2 localizes to the nucleus and interacts with the heterogeneous nuclear ribonucleoprotein scaffold attachment factor-B. Traweger, A., Fuchs, R., Krizbai, I.A., Weiger, T.M., Bauer, H.C., Bauer, H. J. Biol. Chem. (2003) [Pubmed]
  15. Thyroid morphology and function in adults with untreated isolated growth hormone deficiency. Alcântara, M.R., Salvatori, R., Alcântara, P.R., Nóbrega, L.M., Campos, V.S., Oliveira, E.C., Oliveira, M.H., Souza, A.H., Aguiar-Oliveira, M.H. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  16. Scaffold attachment factor SAFB1 suppresses estrogen receptor alpha-mediated transcription in part via interaction with nuclear receptor corepressor. Jiang, S., Meyer, R., Kang, K., Osborne, C.K., Wong, J., Oesterreich, S. Mol. Endocrinol. (2006) [Pubmed]
  17. Identification of proteins binding to E-Box/Ku86 sites and function of the tumor suppressor SAFB1 in transcriptional regulation of the human xanthine oxidoreductase gene. Lin, J., Xu, P., LaVallee, P., Hoidal, J.R. J. Biol. Chem. (2008) [Pubmed]
  18. Inhibition of oestrogen receptor activity by the co-repressor HET/SAF-B is relieved by blockade of histone deacetylase activity. Oesterreich, S., Zhang, Q.P., Lee, A.V. Eur. J. Cancer (2000) [Pubmed]
  19. A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D. Arao, Y., Kuriyama, R., Kayama, F., Kato, S. Arch. Biochem. Biophys. (2000) [Pubmed]
  20. Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B. Nikolakaki, E., Kohen, R., Hartmann, A.M., Stamm, S., Georgatsou, E., Giannakouros, T. J. Biol. Chem. (2001) [Pubmed]
  21. Purification and molecular cloning of the scaffold attachment factor B (SAF-B), a novel human nuclear protein that specifically binds to S/MAR-DNA. Renz, A., Fackelmayer, F.O. Nucleic Acids Res. (1996) [Pubmed]
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