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Gene Review

BIRC6  -  baculoviral IAP repeat containing 6

Homo sapiens

Synonyms: APOLLON, BIR repeat-containing ubiquitin-conjugating enzyme, BRUCE, Baculoviral IAP repeat-containing protein 6, KIAA1289, ...
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Disease relevance of BIRC6

  • To evaluate the diagnostic potential and hemodynamic significance of exercise-induced multiple-lead QRS changes, we studied exercise test responses in 230 patients with chest pain syndromes undergoing Bruce protocol exercise tests [1].
  • Among the 21 patients without previous myocardial infarction, the 12 with a low ischemic threshold, which occurred during the first three steps of the modified Bruce protocol, had an anaerobic threshold significantly lower than the other nine patients (13.1 +/- 1.5 versus 14.9 +/- 1.0 ml/kg per minute VO2, p less than 0.01) [2].
  • A significantly higher heart rate at onset of ischemia was seen during Bruce protocol exercise testing than during daily life (117 +/- 12 versus 95 +/- 15 beats/min, p less than 0.01) [3].
  • Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied [4].
  • METHODS AND RESULTS: In this prospective cohort investigation, 1575 male participants (mean age, 43 years) in the Framingham Offspring Study who were free of coronary heart disease, who were not taking beta-blockers, and who underwent submaximal treadmill exercise testing (Bruce protocol) were studied [5].

Psychiatry related information on BIRC6

  • Since 1976, when Morales, Eidinger and Bruce first published on the treatment of human urothelial bladder cancer, bacillus Calmette-Guérin has gained worldwide acceptance as a therapy against bladder carcinoma recurrences [6].
  • Recently, Leder and Bruce (2000, Quarterly Journal of Experimental Psychology A 53 513-536) argued that configural information in face processing consists at least partly of locally processed relations between facial elements [7].
  • A neural spike count rule has been presented for both threshold and intensity discrimination under the assumption that auditory perception occurs via integration over a relatively long time period (Bruce et al., 1999) [8].
  • The physical activity challenge consisted of a Maximal effort trial (VO2 max) following the Bruce protocol on a walking treadmill [9].
  • We modified Bruce, Dolan, and Phillips-Grant's (2000) threshold procedure for determining the wane of childhood amnesia [10].

High impact information on BIRC6

  • In the presence of an exogenous E2, UbcH5c, purified Nrdp1 catalyzes BRUCE ubiquitination [11].
  • Thus, BRUCE normally inhibits apoptosis, and Nrdp1 can be important in the initiation of apoptosis by catalyzing ubiquitination and degradation of BRUCE [11].
  • METHODS AND RESULTS: After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order) [12].
  • We also evaluated blood pressure responses during erect treadmill exercise (Bruce protocol) [13].
  • METHODS AND RESULTS: We performed exercise (maximal treadmill Bruce protocol), dobutamine (up to 40 micrograms/kg per minute) and dipyridamole (up to 0.84 mg/kg over 10 minutes) stress echocardiography tests, in random sequence and on separate days, in 136 consecutive patients [14].

Chemical compound and disease context of BIRC6

  • METHODS: We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG [15].
  • A randomized, double-blind, placebo-controlled study in patients with clinical symptoms of stable angina pectoris and healed myocardial infarction (n = 22) has shown that oral supplementation with L-arginine (6 g/day for 3 days) increases exercise capacity (tested on a Marquette case 12 treadmill according to the modified Bruce protocol) [16].
  • METHODS: Twenty-four patients (18 males and 6 females, age 59+/-9 years) with heart disease underwent symptom-limited treadmill exercise testing according to the Bruce protocol, and BRS was measured utilizing the phenylephrine method [17].
  • In all subjects tachycardia was induced by 1) administration of atropine (1 mg bolus IV), 2) administration of isoprenaline (0.5-0.25 micrograms/min IV) and 3) treadmill exercise test according to Bruce protocol [18].
  • Similarly, on the Multigating Substance Use Evaluation System (Jurkovic & Bruce, 1991), the suicidal youth were at a high risk for alcohol and drug abuse [19].

Biological context of BIRC6


Anatomical context of BIRC6

  • (S. Funahashi, C.J. Bruce and P.S. Goldman-Rakic, Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol 61:331-349, 1989) [24].
  • However, a strongly positive exercise electrocardiogram in the first two stages of the Bruce protocol or at a heart rate of less than 140 beats/min was related to the extent of coronary artery disease and impaired myocardial perfusion, and identified patients with more extensive coronary artery disease and jeopardized myocardium [25].
  • Detection and transduction of pheromonal signals by the mouse vomeronasal organ (VNO) is critical for the formation of a persistent memory required for mate recognition in the context of selective pregnancy failure (the Bruce effect) [26].
  • In 1956, Bruce Glick and Timothy Chang reported that the bursa of Fabricius plays an important role in antibody production [27].
  • The contribution of Bruce Glick to the definition of the role played by the bursa of Fabricius in the development of the B cell lineage [27].

Associations of BIRC6 with chemical compounds

  • Forty-nine normotensive chronic cocaine abusers underwent Bruce protocol treadmill exercise testing until they attained 85% maximum predicted heart rate [28].
  • METHODS: Study population consisted of 168 (138 male, 30 female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10 min) stress echocardiography tests were performed [29].
  • Two exercise tests using the Bruce protocol with technetium-99m (99mTc)-sestamibi were performed on consecutive days in a randomized order [30].
  • METHODS: In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose [31].
  • Zatebradine reduced rest heart rate both at 4 weeks ([mean +/- SEM] 12.9 +/- 1.23 vs. 2.3 +/- 1.6 [placebo] beats/min, p < 0.0001) and at the end of comparable stages of Bruce exercise (16.7 +/- 1.2 vs. 3.4 +/- 1.2 [placebo] beats/min, p < 0.0001) [32].

Enzymatic interactions of BIRC6

  • In response to apoptotic stimuli, BRUCE is degraded by proteasomes and/or cleaved by caspases and HtrA2 depending on the specific stimulus and the cell type [20].

Regulatory relationships of BIRC6

  • Through these associations, BRUCE promotes the degradation of Smac and inhibits the activity of caspase-9 but not the effector caspase, caspase-3 [20].
  • In vivo, overexpression of Nrdp1 promotes ubiquitination and proteasomal degradation of BRUCE [11].
  • In Section III Dr. Bruce Cheson describes recent progress in inhibiting cell cycle progression by selectively disrupting cyclin D1 with structurally unique compounds such as flavopiridol in mantle cell lymphoma as well as describing a new class of agents that affect proteasome degradation pathways [33].

Other interactions of BIRC6


Analytical, diagnostic and therapeutic context of BIRC6

  • Treadmill exercise tests were also performed on a separate occasion with the Bruce protocol [39].
  • Each patient underwent exercise electrocardiography (Bruce protocol) that was interpreted as abnormal if the ST segment developed 0.1-mV or greater depression 80 msec after the J point [40].
  • To determine the value of a multivariate approach for the analysis of the treadmill exercise tolerance test (ETT), 237 patients referred for evaluation of chest pain who underwent a standard Bruce protocol ETT and coronary arteriography were studied [41].
  • In 107 patients who survived 3 months, cardiac function was assessed at 1 week by resting hemodynamics and at 3 months by treadmill testing (Bruce protocol), supine rest and exercise radionuclide angiography, and supine rest and exercise right-heart hemodynamics [42].
  • In all patients, a Bruce exercise test with the simultaneous recording of leads I, II, V4R, V1, V4 and V6 was followed by coronary angiography [43].


  1. Multiple-lead QRS changes with exercise testing. Diagnostic value and hemodynamic implications. Berman, J.L., Wynne, J., Cohn, P.F. Circulation (1980) [Pubmed]
  2. Anaerobic threshold in patients with exercise-induced myocardial ischemia. Fortini, A., Bonechi, F., Taddei, T., Gensini, G.F., Malfanti, P.L., Neri Serneri, G.G. Circulation (1991) [Pubmed]
  3. Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease. McLenachan, J.M., Weidinger, F.F., Barry, J., Yeung, A., Nabel, E.G., Rocco, M.B., Selwyn, A.P. Circulation (1991) [Pubmed]
  4. Effect of bepridil in patients with chronic stable angina: results of a multicenter trial. Hill, J.A., O'Brien, J.T., Alpert, J.S., Gore, J.M., Zusman, R.M., Christensen, D., Boucher, C.A., Vetrovec, G., Borer, J.S., Friedman, C. Circulation (1985) [Pubmed]
  5. Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study. Lauer, M.S., Okin, P.M., Larson, M.G., Evans, J.C., Levy, D. Circulation (1996) [Pubmed]
  6. Prospects for improving the efficacy of BCG. Böhle, A. Eur. Urol. (1992) [Pubmed]
  7. Configural features in the context of upright and inverted faces. Leder, H., Candrian, G., Huber, O., Bruce, V. Perception. (2001) [Pubmed]
  8. Predicting the threshold of pulse-train electrical stimuli using a stochastic auditory nerve model: the effects of stimulus noise. Xu, Y., Collins, L.M. IEEE transactions on bio-medical engineering. (2004) [Pubmed]
  9. A maximal effort trial in obese women carrying the beta2-adrenoceptor Gln27Glu polymorphism. Macho-Azcárate, T., Calabuig, J., Martí, A., Martínez, J.A. Journal of physiology and biochemistry. (2002) [Pubmed]
  10. The wane of childhood amnesia for autobiographical and public event memories. Multhaup, K.S., Johnson, M.D., Tetirick, J.C. Memory (Hove, England) (2005) [Pubmed]
  11. Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis. Qiu, X.B., Markant, S.L., Yuan, J., Goldberg, A.L. EMBO J. (2004) [Pubmed]
  12. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Rosano, G.M., Leonardo, F., Pagnotta, P., Pelliccia, F., Panina, G., Cerquetani, E., della Monica, P.L., Bonfigli, B., Volpe, M., Chierchia, S.L. Circulation (1999) [Pubmed]
  13. Abnormal forearm vascular responses during dynamic leg exercise in patients with vasovagal syncope. Thomson, H.L., Lele, S.S., Atherton, J.J., Wright, K.N., Stafford, W., Frenneaux, M.P. Circulation (1995) [Pubmed]
  14. Stress echocardiography in the detection of myocardial ischemia. Head-to-head comparison of exercise, dobutamine, and dipyridamole tests. Beleslin, B.D., Ostojic, M., Stepanovic, J., Djordjevic-Dikic, A., Stojkovic, S., Nedeljkovic, M., Stankovic, G., Petrasinovic, Z., Gojkovic, L., Vasiljevic-Pokrajcic, Z. Circulation (1994) [Pubmed]
  15. A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates. Bogaty, P., Guimond, J., Robitaille, N.M., Rousseau, L., Simard, S., Rouleau, J.R., Dagenais, G.R. J. Am. Coll. Cardiol. (1997) [Pubmed]
  16. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Ceremuzyński, L., Chamiec, T., Herbaczyńska-Cedro, K. Am. J. Cardiol. (1997) [Pubmed]
  17. Impaired baroreflex as a cause of chronotropic incompetence during exercise via autonomic mechanism in patients with heart disease. Fukuma, N., Oikawa, K., Aisu, N., Kato, K., Kimura-Kato, Y.K., Tuchida, T., Mabuchi, K., Takano, T. International journal of cardiology. (2004) [Pubmed]
  18. Alterations of first derivative of apexcardiogram indices during induced changes of heart rate. Boudonas, G., Lefkos, N., Efthimiadis, A., Styliadis, I.G., Aroditis, K. Acta cardiologica. (1993) [Pubmed]
  19. The role of drugs and alcohol in urban minority adolescent suicide attempts. Jones, G.D. Death studies. (1997) [Pubmed]
  20. The membrane-associated inhibitor of apoptosis protein, BRUCE/Apollon, antagonizes both the precursor and mature forms of Smac and caspase-9. Qiu, X.B., Goldberg, A.L. J. Biol. Chem. (2005) [Pubmed]
  21. Prognostic value of exercise testing, coronary angiography and left ventriculography 6--8 weeks after myocardial infarction. De Feyter, P.J., van Eenige, M.J., Dighton, D.H., Visser, F.C., de Jong, J., Roos, J.P. Circulation (1982) [Pubmed]
  22. Left ventricular geometry and function in adults with Ebstein's anomaly of the tricuspid valve. Benson, L.N., Child, J.S., Schwaiger, M., Perloff, J.K., Schelbert, H.R. Circulation (1987) [Pubmed]
  23. Ca2+-dependent protein kinase--a modulation of the plasma membrane Ca2+-ATPase in parotid acinar cells. Bruce, J.I., Yule, D.I., Shuttleworth, T.J. J. Biol. Chem. (2002) [Pubmed]
  24. Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model. Compte, A., Brunel, N., Goldman-Rakic, P.S., Wang, X.J. Cereb. Cortex (2000) [Pubmed]
  25. Hemodynamic, angiographic and scintigraphic correlates of positive exercise electrocardiograms: emphasis on strongly positive exercise electrocardiograms. Colby, J., Hakki, A.H., Iskandrian, A.S., Mattleman, S. J. Am. Coll. Cardiol. (1983) [Pubmed]
  26. Pheromonal recognition memory induced by TRPC2-independent vomeronasal sensing. Kelliher, K.R., Spehr, M., Li, X.H., Zufall, F., Leinders-Zufall, T. Eur. J. Neurosci. (2006) [Pubmed]
  27. The contribution of Bruce Glick to the definition of the role played by the bursa of Fabricius in the development of the B cell lineage. Ribatti, D., Crivellato, E., Vacca, A. Clin. Exp. Immunol. (2006) [Pubmed]
  28. Exaggerated pressor response to treadmill exercise in chronic cocaine abusers with left ventricular hypertrophy. Cigarroa, C.G., Boehrer, J.D., Brickner, M.E., Eichhorn, E.J., Grayburn, P.A. Circulation (1992) [Pubmed]
  29. Integrated evaluation of relation between coronary lesion features and stress echocardiography results: the importance of coronary lesion morphology. Beleslin, B.D., Ostojic, M., Djordjevic-Dikic, A., Babic, R., Nedeljkovic, M., Stankovic, G., Stojkovic, S., Marinkovic, J., Nedeljkovic, I., Stepanovic, J., Saponjski, J., Petrasinovic, Z., Nedeljkovic, S., Kanjuh, V. J. Am. Coll. Cardiol. (1999) [Pubmed]
  30. Effect of a standardized meal on the threshold of exercise-induced myocardial ischemia in patients with stable angina. Colles, P., Juneau, M., Grégoire, J., Larivée, L., Desideri, A., Waters, D. J. Am. Coll. Cardiol. (1993) [Pubmed]
  31. The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease. Thadani, U., Smith, W., Nash, S., Bittar, N., Glasser, S., Narayan, P., Stein, R.A., Larkin, S., Mazzu, A., Tota, R., Pomerantz, K., Sundaresan, P. J. Am. Coll. Cardiol. (2002) [Pubmed]
  32. Addition of zatebradine, a direct sinus node inhibitor, provides no greater exercise tolerance benefit in patients with angina taking extended-release nifedipine: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The Zatebradine Study Group. Frishman, W.H., Pepine, C.J., Weiss, R.J., Baiker, W.M. J. Am. Coll. Cardiol. (1995) [Pubmed]
  33. Rational approaches to design of therapeutics targeting molecular markers. Klasa, R.J., List, A.F., Cheson, B.D. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program. (2001) [Pubmed]
  34. Cachectin--Tumour necrosis factor: a cytokine that mediates injury initiated by invasive parasites. Beutler, B., Cerami, A. Parasitol. Today (Regul. Ed.) (1987) [Pubmed]
  35. Six-year experience with graded exercise testing in a model family practice office. Zoller, D.P., Boyd, G.E. The Journal of family practice. (1985) [Pubmed]
  36. Comparison of the Asymptomatic Cardiac Ischemia Pilot and modified Asymptomatic Cardiac Ischemia Pilot versus Bruce and Cornell exercise protocols. Tamesis, B., Stelken, A., Byers, S., Shaw, L., Younis, L., Miller, D.D., Chaitman, B.R. Am. J. Cardiol. (1993) [Pubmed]
  37. The differential response in atrial natriuretic peptide release during exercise in patients with and without ischemic heart disease. Hu, D.C., Wong, E.F., Wong, N.L. Am. J. Med. Sci. (1988) [Pubmed]
  38. Relationship between pulmonary function and exercise tolerance in patients with ankylosing spondylitis. Seçkin, U., Bölükbasi, N., Gürsel, G., Eröz, S., Sepici, V., Ekim, N. Clinical and experimental rheumatology. (2000) [Pubmed]
  39. Blood pressure during normal daily activities, sleep, and exercise. Comparison of values in normal and hypertensive subjects. Pickering, T.G., Harshfield, G.A., Kleinert, H.D., Blank, S., Laragh, J.H. JAMA (1982) [Pubmed]
  40. Accuracy of exercise electrocardiography in detecting physiologically significant coronary arterial lesions. Wilson, R.F., Marcus, M.L., Christensen, B.V., Talman, C., White, C.W. Circulation (1991) [Pubmed]
  41. A multivariate approach for interpreting treadmill exercise tests in coronary artery disease. Berman, J.L., Wynne, J., Cohn, P.F. Circulation (1978) [Pubmed]
  42. Cardiac allograft ischemic time. Relation to graft survival and cardiac function. Pflugfelder, P.W., Thomson, D., Singh, N.R., Menkis, A.H., McKenzie, F.N., Kostuk, W.J. Circulation (1989) [Pubmed]
  43. Value of lead V4R in exercise testing to predict proximal stenosis of the right coronary artery. Braat, S.H., Kingma, J.H., Brugada, P., Wellens, H.J. J. Am. Coll. Cardiol. (1985) [Pubmed]
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