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Gene Review

SPEN  -  spen family transcriptional repressor

Homo sapiens

Synonyms: HIAA0929, KIAA0929, MINT, Msx2-interacting protein, RBM15C, ...
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Disease relevance of SPEN

  • Three 1 microgram or 2 micrograms doses of Merck, Sharp and Dohme plasma vaccine were given to 119 infants of mothers negative for antibody to hepatitis B surface antigen (anti-HBs) [1].
  • One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen [2].
  • Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002) [3].
  • METHODS: A random sample of patients with early RA, for whom sequential hand radiographs and Sharp scores were available, was selected from the National Data Bank for Rheumatic Diseases [4].
  • METHODS: Wrist/hand radiographs of 25 patients with polyarthritis obtained at first observation and then yearly for 4-5 years were assessed independently by 2 pediatric rheumatologists according to the Sharp and Larsen methods [5].

High impact information on SPEN

  • Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale [6].
  • Neuroscience. Sharp edges into new terrain. Interview by Andrew Lawler [7].
  • These findings suggest that the conserved function of the SPOC domain is to mediate interaction with SMRT/NCoR corepressors, and that Spen proteins play an essential role in the repression complex [8].
  • A recent study by Sharp et al.((1)) sheds further light on the subject by exploiting the genetics and cytology of the fruit fly embryo [9].
  • Recent reports have shown that Decadron (dexamethasone; Merck Sharp & Dohme, West Point, Pa) has a significant antiemetic effect on cisplatin-induced vomiting [10].

Chemical compound and disease context of SPEN

  • In 1982, the Centers for Disease Control, the Food and Drug Administration, and the manufacturer created a surveillance system to monitor spontaneous reports of adverse events occurring after inoculation with the new plasma-derived hepatitis B vaccine (Heptavax-B, Merck Sharp and Dohme, West Point, PA) [11].
  • By using cell morphology, arginine dihydrolase, and gas production in de Man, Sharp, Rogosa broth, 122 isolates of vancomycin-resistant lactic bacteria from humans were assigned to five profiles, allowing us to distinguish Pediococcus, homofermentative and heterofermentative Lactobacillus, and Leuconostoc species [12].
  • We present baseline bone densitometry from the Early Postmenopausal Interventional Cohort study (EPIC, sponsored by Merck, Sharp & Dohme) for the first time, in which 1609 women from England, Oregon, Hawaii and Denmark are participating to investigate the efficacy of daily oral alendronate to prevent early postmenopausal bone loss [13].
  • The presence of polymerized human serum albumin receptors (pHSA-R) in two hepatitis B virus (HBV) plasma derived vaccines (HB-Vax, Merck Sharp and Dohme; Hevac-B, Pasteur) was detected by three methods, using pHSA polystyrene coated beads and 125I-anti-HBs (method 1) and polyclonal (method 2) or monoclonal (method 3) peroxidase conjugated anti-HBs [14].
  • These bactericidal effects against bacteria in saliva and dental plaque indicated that Listerine and Cool Mint Listerine antiseptic are useful in oral cavity as antiseptic mouth rinses [15].

Biological context of SPEN

  • Our results demonstrate that the phenotypes obtained from overexpressing NITO share striking similarity to those associated with loss of spen [16].
  • The region of the genome reiterated in these molecules is that which has been implicated in transformation of rat cells by adenovirus (Gallimore, Sharp, and Sambrook, 1974; Graham, van der Eb, and Heijneker, 1974) [17].
  • The RNA-binding properties of this protein were analyzed in an immunoprecipitation assay with the 100K-specific monoclonal antibody 2100K-1 (C. L. Cepko and P. A. Sharp, Virology 129:137-154, 1983) [18].
  • Crystallographic data (to 1.8 A) for the R172A variant indicate that the molecular structure of the proposed [Sharp, K. H., et al. (2004) Biochemistry 43, 8644-8651] proton transfer pathway from the ascorbate to the heme is conserved, which accounts for the residual activity [19].
  • No adverse effect upon cognitive function has been detected during the first 9 months of treatment by a thiazide diuretic (Moduretic; Merck Sharp & Dohme, Hoddesdon, UK) or a beta-blocking agent (atenolol) of moderately elevated blood pressure in a cohort of 2630 men and women aged between 65 and 74 years [20].

Anatomical context of SPEN

  • A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44) [3].
  • After brief reviews on how to score radiographs using the Larsen and Sharp method, photographic slides of metacarpophalangeal joints of 2 patients were shown [21].
  • Solid and papillary epithelial neoplasms of the pancreas (SPENP) are extremely rare and usually affect young women [22].
  • Diagnostic criteria for primary osteoarthritis of the hip joint in the Japanese population were determined by the roentgenographic measurements of the center-edge (CE) angle, the Sharp angle, and the acetabular roof obliquity in 254 normal hips [23].
  • 4. Sharp edges in hSCLLs, branching membranes and stable membrane stacks were explained by the presence of ceramides, the major components and structural elements of human stratum corneum lipids (hSCLs) [24].

Associations of SPEN with chemical compounds

  • At 2 years, the median and interquartile range (IQR) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group (1.8 [IQR 0.5-6.0] versus 3.5 [IQR 0.5-10]; P = 0.019) [25].
  • In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients [26].
  • Ammonium sulfate also enhances transcription from the adeno IVa2 promoter, which is not expressed in extracts that lack (NH4)2SO4 (Fire, A., Baker, C. C., Manley, J. L., Ziff, E. B., and Sharp, P. A. (1981) J. Virol. 40, 703-719; Lee, D. C., and Roeder, R. G. (1981) Mol. Cell. Biol. 1, 635-651) [27].
  • Other treatments for hyperlipidemia include diet and cholesterol-lowering agents, such as Mevacor (lovastatin; Merck Sharp & Dohme, West Point, PA) [28].
  • Previous work showed that primary root elongation in maize (Zea mays L.) seedlings at low water potentials (psi(w)) requires the accumulation of abscisic acid (ABA) (R.E. Sharp, Y. Wu, G.S. Voetberg, I.N. Saab, M.E. LeNoble [1994] J Exp Bot 45: 1743-1751) [29].

Physical interactions of SPEN

  • The Spen Homolog Msx2-Interacting Nuclear Target Protein Interacts with the E2 Ubiquitin-Conjugating Enzyme UbcH8 [30].

Analytical, diagnostic and therapeutic context of SPEN

  • Fourteen persons required a second booster dose for protection; after vaccination with 400 CCA units of whole-virus vaccine from Merck Sharp and Dohme (West Point, Pa.), 89%-100% of the 14 vaccinees finally achieved HAI titers of greater than or equal to 1:20 [31].
  • This study focuses on the influence of the following 4 factors on radiographic scores according to van der Heijde's modification of the Sharp method: intraobserver variation, interobserver variation, follow-up time, and number of measurement occasions within a patient series [32].
  • A total of 72 hemodialysis patients (mean age, 55.7), received the hepatitis B vaccine (Heptavax-B, Merck Sharp & Dohme, West Point, PA) [33].
  • PARTICIPANTS: Twenty-three subjects and controls from the Sharp Rees-Stealy Hospital and the Shiley Eye Center at the University of California, San Diego. TESTING: Virtual reality-based entoptic perimetry was compared with achromatic threshold perimetry [34].
  • In cross sectional studies, 3 quantitative methods, the Steinbrocker radiographic stage, modified Sharp method, and Larsen method, are highly significantly correlated and yield similar results in comparisons with other clinical measures [35].


  1. Very-low-dose hepatitis B vaccine in newborn infants: an economic option for control in endemic areas. Moyes, C.D., Milne, A., Dimitrakakis, M., Goldwater, P.N., Pearce, N. Lancet (1987) [Pubmed]
  2. Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia. Kantarjian, H.M., Walters, R.S., Keating, M.J., Smith, T.L., O'Brien, S., Estey, E.H., Huh, Y.O., Spinolo, J., Dicke, K., Barlogie, B. J. Clin. Oncol. (1990) [Pubmed]
  3. Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis. McQueen, F.M., Benton, N., Perry, D., Crabbe, J., Robinson, E., Yeoman, S., McLean, L., Stewart, N. Arthritis Rheum. (2003) [Pubmed]
  4. Performance of an automated computer-based scoring method to assess joint space narrowing in rheumatoid arthritis: a longitudinal study. Finckh, A., de Pablo, P., Katz, J.N., Neumann, G., Lu, Y., Wolfe, F., Duryea, J. Arthritis Rheum. (2006) [Pubmed]
  5. Use of the sharp and larsen scoring methods in the assessment of radiographic progression in juvenile idiopathic arthritis. Rossi, F., Di Dia, F., Galip??, O., Pistorio, A., Valle, M., Magni-Manzoni, S., Ruperto, N., Tom??, P., Martini, A., Ravelli, A. Arthritis Rheum. (2006) [Pubmed]
  6. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. Bathon, J.M., Martin, R.W., Fleischmann, R.M., Tesser, J.R., Schiff, M.H., Keystone, E.C., Genovese, M.C., Wasko, M.C., Moreland, L.W., Weaver, A.L., Markenson, J., Finck, B.K. N. Engl. J. Med. (2000) [Pubmed]
  7. Neuroscience. Sharp edges into new terrain. Interview by Andrew Lawler. Sharp, P. Science (2001) [Pubmed]
  8. A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. Ariyoshi, M., Schwabe, J.W. Genes Dev. (2003) [Pubmed]
  9. Dr. Dolittle and the making of the mitotic spindle. Heck, M.M. Bioessays (1999) [Pubmed]
  10. Cataracts induced by intermittent Decadron used as an antiemetic. Bluming, A.Z., Zeegen, P. J. Clin. Oncol. (1986) [Pubmed]
  11. Postmarketing surveillance for neurologic adverse events reported after hepatitis B vaccination. Experience of the first three years. Shaw, F.E., Graham, D.J., Guess, H.A., Milstien, J.B., Johnson, J.M., Schatz, G.C., Hadler, S.C., Kuritsky, J.N., Hiner, E.E., Bregman, D.J. Am. J. Epidemiol. (1988) [Pubmed]
  12. Identification of vancomycin-resistant lactic bacteria isolated from humans. Mackey, T., Lejeune, V., Janssens, M., Wauters, G. J. Clin. Microbiol. (1993) [Pubmed]
  13. Comparison of bone densitometry of the phalanges, distal forearm and axial skeleton in early postmenopausal women participating in the EPIC Study. Ravn, P., Overgaard, K., Huang, C., Ross, P.D., Green, D., McClung, M. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (1996) [Pubmed]
  14. Receptors for polymerized human serum albumin in plasma derived hepatitis B vaccines. Mora, I., Porres, J.C., Carreño, V. Vaccine (1987) [Pubmed]
  15. Bactericidal effects of mouth rinses on oral bacteria. Kasuga, Y., Ikenoya, H., Okuda, K. Bull. Tokyo Dent. Coll. (1997) [Pubmed]
  16. Characterization of the split ends-like gene spenito reveals functional antagonism between SPOC family members during Drosophila eye development. Jemc, J., Rebay, I. Genetics (2006) [Pubmed]
  17. Genome structure of incomplete particles of adenovirus. Daniell, E. J. Virol. (1976) [Pubmed]
  18. RNA-binding properties of a translational activator, the adenovirus L4 100-kilodalton protein. Riley, D., Flint, S.J. J. Virol. (1993) [Pubmed]
  19. Interaction of ascorbate peroxidase with substrates: a mechanistic and structural analysis. Macdonald, I.K., Badyal, S.K., Ghamsari, L., Moody, P.C., Raven, E.L. Biochemistry (2006) [Pubmed]
  20. Treating hypertension in the older person: an evaluation of the association of blood pressure level and its reduction with cognitive performance. Bird, A.S., Blizard, R.A., Mann, A.H. J. Hypertens. (1990) [Pubmed]
  21. A practical exercise in reading RA radiographs by the larsen and sharp methods. Molenaar, E.T., Edmonds, J., Boers, M., van der Heijde, D.M., Lassere, M. J. Rheumatol. (1999) [Pubmed]
  22. Solid and papillary epithelial neoplasms of the pancreas: aggressive resection for cure. Yoon, D.Y., Hines, O.J., Bilchik, A.J., Lewin, K., Cortina, G., Reber, H.A. The American surgeon. (2001) [Pubmed]
  23. Primary osteoarthritis of the hip joint in Japan. Nakamura, S., Ninomiya, S., Nakamura, T. Clin. Orthop. Relat. Res. (1989) [Pubmed]
  24. Energy-filtered cryotransmission electron microscopy of liposomes prepared from human stratum corneum lipids. Schmidtgen, M.C., Drechsler, M., Lasch, J., Schubert, R. Journal of microscopy. (1998) [Pubmed]
  25. Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial. Svensson, B., Boonen, A., Albertsson, K., van der Heijde, D., Keller, C., Hafström, I. Arthritis Rheum. (2005) [Pubmed]
  26. Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage. Lard, L.R., Boers, M., Verhoeven, A., Vos, K., Visser, H., Hazes, J.M., Zwinderman, A.H., Schreuder, G.M., Breedveld, F.C., De Vries, R.R., van der Linden, S., Zanelli, E., Huizinga, T.W. Arthritis Rheum. (2002) [Pubmed]
  27. Preferential stimulation of transcription from simian virus 40 late and adeno IVa2 promoters in a HeLa cell extract. Natarajan, V., Madden, M.J., Salzman, N.P. J. Biol. Chem. (1983) [Pubmed]
  28. Hyperlipidemia and transplantation: etiologic factors and therapy. Pirsch, J.D., D'Alessandro, A.M., Sollinger, H.W., Knechtle, S.J., Reed, A., Kalayoglu, M., Belzer, F.O. J. Am. Soc. Nephrol. (1992) [Pubmed]
  29. Abscisic acid accumulation maintains maize primary root elongation at low water potentials by restricting ethylene production. Spollen, W.G., LeNoble, M.E., Samuels, T.D., Bernstein, N., Sharp, R.E. Plant Physiol. (2000) [Pubmed]
  30. The Spen Homolog Msx2-Interacting Nuclear Target Protein Interacts with the E2 Ubiquitin-Conjugating Enzyme UbcH8. Li, J., Wang, J., Yang, X., Li, J., Qin, H., Dong, X., Zhu, Y., Liang, L., Liang, Y., Han, H. Mol. Cell. Biochem. (2006) [Pubmed]
  31. Sequential immunization of laboratory personnel with influenza A/New Jersey/76 split- and whole-virus vaccines. Edelman, R., Scheidt, K.B. J. Infect. Dis. (1977) [Pubmed]
  32. Modified sharp method: factors influencing reproducibility and variability. Swinkels, H.L., Laan, R.F., van 't Hof, M.A., van der Heijde, D.M., de Vries, N., van Riel, P.L. Semin. Arthritis Rheum. (2001) [Pubmed]
  33. Long-term evaluation of the hepatitis B vaccine (Heptavax-B) in hemodialysis patients. Pasko, M.T., Bartholomew, W.R., Beam, T.R., Amsterdam, D., Cunningham, E.E. Am. J. Kidney Dis. (1988) [Pubmed]
  34. Correlation between static automated and scanning laser entoptic perimetry in normal subjects and glaucoma patients. Plummer, D.J., Lopez, A., Azen, S.P., LaBree, L., Bartsch, D.U., Sadun, A.A., Freeman, W.R. Ophthalmology (2000) [Pubmed]
  35. Quantitative analysis of hand radiographs in rheumatoid arthritis: time course of radiographic changes, relation to joint examination measures, and comparison of different scoring methods. Pincus, T., Callahan, L.F., Fuchs, H.A., Larsen, A., Kaye, J. J. Rheumatol. (1995) [Pubmed]
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