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Gene Review

RYBP  -  RING1 and YY1 binding protein

Homo sapiens

Synonyms: AAP1, APAP-1, Apoptin-associating protein 1, DED-associated factor, DEDAF, ...
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Disease relevance of RYBP


Psychiatry related information on RYBP

  • There was no significant (p = 0.05) difference between mean AHI indices, sleep stages, sleep stage shifts, and snore arousals for CPAP night and APAP night [6].
  • Alcohol consumption also causes the induction of P450IIE1, a liver microsomal enzyme that in reconstitution studies has proven to be an effective catalyst of APAP oxidation [7].
  • The tramadol/APAP group had significant improvements on the role-physical (P = 0.005), bodily pain (P = 0.046), role-emotional (P = 0.001), mental health (P = 0.026), reported health transition (P = 0.038), and mental component summary (P = 0.008) subscales of the SF-36 [8].
  • Autoadjusting CPAP devices (APAP) are designed to continuously adjust the positive pressure to the required levels, and thus increase treatment quality and patient compliance [9].

High impact information on RYBP

  • At later time points (8-12 hours), APAP-treated mice that were maintained at normothermia manifested increased hepatocyte apoptosis, as assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining and cleavage of poly(adenosine diphosphate-ribose) polymerase [2].
  • CONCLUSIONS: Mild hypothermia improved survival and attenuated liver injury and apoptosis in APAP-treated mice by reducing hepatic congestion and improving glycogen recovery without affecting hepatic regeneration [2].
  • RESULTS: Mild hypothermia resulted in improved survival after APAP intoxication [2].
  • Therefore, we investigated the effects of body temperature on the progression of APAP-induced liver injury in mice [2].
  • Among hepatic nonparenchymal inflammatory cells, we examined the role of the abundant natural killer (NK) cells and NK cells with T-cell receptors (NKT cells) in APAP-induced liver injury [10].

Chemical compound and disease context of RYBP


Biological context of RYBP


Anatomical context of RYBP


Associations of RYBP with chemical compounds

  • In studies designed to simulate a clinical observation in which an individual became tolerant to normally lethal doses of acetaminophen (APAP), mice were pretreated with increasing doses of APAP for 8 days and challenged on day 9 with normally supralethal doses of APAP [18].
  • Susceptibility is presumably caused by induction of cytochrome P-4502EI by ethanol and by depletion of glutathione (GSH) because of the effects of alcohol, the malnutrition often associated with alcoholism, and the depletion associated with chronic use of APAP and impaired glucuronidation caused by fasting perhaps as well [22].
  • APAP treatment led to increased liver damage and decreased hepatic glutathione levels in the hyposulfatemic Nas1-null mice compared with that in normosulfatemic wild-type mice [5].
  • Even when given 8 hours after APAP dose, leflunomide still protected from massive liver necrosis [3].
  • The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), that leads to gluthatione depletion has been suspected to be the main effector of hepatocyte apoptosis during APAP-induced ALF [4].

Physical interactions of RYBP

  • By using yeast three-hybrid assay, we demonstrated that hGABP beta and YY1 formed a complex only in the presence of YEAF1, indicating that YEAF1 is a bridging factor of these two transcription factors [19].
  • Mapping studies indicate that RYBP binds within the known "repression domain" of E2F6 [23].

Regulatory relationships of RYBP

  • These cofactors are functionally different in that YAF-2 positively regulates the transcriptional activity of hGABP but YEAF1 negatively regulates this activity [19].

Other interactions of RYBP

  • Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function [24].
  • We report the isolation of RYBP, a recently identified member of the mammalian polycomb complex, as an E2F6-interacting protein [23].
  • In the nucleus, DEDAF caused the DEDD protein to relocalize from subnuclear structures to a diffuse distribution in the nucleoplasm [21].

Analytical, diagnostic and therapeutic context of RYBP

  • A direct evidence of ROS generation was provided by flow cytometry of isolated hepatocytes incubated with APAP [4].
  • Thirty subjects with chronic moderate to severe pain who were receiving oxycodone/acetaminophen (oxy/APAP) for analgesia were initially evaluated for at least 7 days for oxy/APAP requirements for pain control [25].
  • Comparison of mean differences before and after treatment with ibuprofen or placebo indicated a marked decrease in oxy/APAP use with ibuprofen (p less than 0.01) and a slight increase in use in the placebo group [25].
  • STUDY OBJECTIVES: This paper compares the performance of an experimental nasal positive airway pressure device that automatically adjusts the level of applied pressure (APAP) with the performance of a conventional continuous positive airway pressure (CPAP) in a sleep laboratory study [6].
  • At this time only a few studies have evaluated initial titration with APAP in CPAP-naïve patients in an unattended setting [13].


  1. Variability in the expression of polycomb proteins in different normal and tumoral tissues. A pilot study using tissue microarrays. Sánchez-Beato, M., Sánchez, E., González-Carreró, J., Morente, M., Díez, A., Sánchez-Verde, L., Martín, M.C., Cigudosa, J.C., Vidal, M., Piris, M.A. Mod. Pathol. (2006) [Pubmed]
  2. Mild hypothermia attenuates liver injury and improves survival in mice with acetaminophen toxicity. Vaquero, J., Bélanger, M., James, L., Herrero, R., Desjardins, P., Côté, J., Blei, A.T., Butterworth, R.F. Gastroenterology (2007) [Pubmed]
  3. Mitochondrial protection by the JNK inhibitor leflunomide rescues mice from acetaminophen-induced liver injury. Latchoumycandane, C., Goh, C.W., Ong, M.M., Boelsterli, U.A. Hepatology (2007) [Pubmed]
  4. Detoxification of reactive oxygen species by a nonpeptidyl mimic of superoxide dismutase cures acetaminophen-induced acute liver failure in the mouse. Ferret, P.J., Hammoud, R., Tulliez, M., Tran, A., Trébéden, H., Jaffray, P., Malassagne, B., Calmus, Y., Weill, B., Batteux, F. Hepatology (2001) [Pubmed]
  5. Disruption of NaS1 sulfate transport function in mice leads to enhanced acetaminophen-induced hepatotoxicity. Lee, S., Dawson, P.A., Hewavitharana, A.K., Shaw, P.N., Markovich, D. Hepatology (2006) [Pubmed]
  6. A sleep laboratory evaluation of an automatic positive airway pressure system for treatment of obstructive sleep apnea. Behbehani, K., Yen, F.C., Lucas, E.A., Burk, J.R. Sleep. (1998) [Pubmed]
  7. Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2. Raucy, J.L., Lasker, J.M., Lieber, C.S., Black, M. Arch. Biochem. Biophys. (1989) [Pubmed]
  8. Tramadol/acetaminophen combination tablets for the treatment of chronic lower back pain: a multicenter, randomized, double-blind, placebo-controlled outpatient study. Ruoff, G.E., Rosenthal, N., Jordan, D., Karim, R., Kamin, M. Clinical therapeutics. (2003) [Pubmed]
  9. Auto-CPAP therapy based on the forced oscillation technique. Ficker, J.H., Clarenbach, C.F., Neukirchner, C., Fuchs, F.S., Wiest, G.H., Schahin, S.P., Harsch, I.A., Hahn, E.G. Biomedizinische Technik. Biomedical engineering. (2003) [Pubmed]
  10. Innate immune system plays a critical role in determining the progression and severity of acetaminophen hepatotoxicity. Liu, Z.X., Govindarajan, S., Kaplowitz, N. Gastroenterology (2004) [Pubmed]
  11. Opioid and opioid-like drug effects on whole-gut transit measured by scintigraphy. Maurer, A.H., Krevsky, B., Knight, L.C., Brown, K. J. Nucl. Med. (1996) [Pubmed]
  12. Ethanol binging exacerbates sinusoidal endothelial and parenchymal injury elicited by acetaminophen. McCuskey, R.S., Bethea, N.W., Wong, J., McCuskey, M.K., Abril, E.R., Wang, X., Ito, Y., DeLeve, L.D. J. Hepatol. (2005) [Pubmed]
  13. The use of auto-titrating continuous positive airway pressure for treatment of adult obstructive sleep apnea. An American Academy of Sleep Medicine review. Berry, R.B., Parish, J.M., Hartse, K.M. Sleep. (2002) [Pubmed]
  14. Comparison of S-Adenosyl-L-methionine and N-Acetylcysteine Protective Effects on Acetaminophen Hepatic Toxicity. Terneus, M.V., Kiningham, K.K., Carpenter, A.B., Sullivan, S.B., Valentovic, M.A. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  15. Kinetics of acetaminophen glucuronidation by UDP-glucuronosyltransferases 1A1, 1A6, 1A9 and 2B15. Potential implications in acetaminophen-induced hepatotoxicity. Mutlib, A.E., Goosen, T.C., Bauman, J.N., Williams, J.A., Kulkarni, S., Kostrubsky, S. Chem. Res. Toxicol. (2006) [Pubmed]
  16. RYBP, a new repressor protein that interacts with components of the mammalian Polycomb complex, and with the transcription factor YY1. García, E., Marcos-Gutiérrez, C., del Mar Lorente, M., Moreno, J.C., Vidal, M. EMBO J. (1999) [Pubmed]
  17. Human death effector domain-associated factor interacts with the viral apoptosis agonist Apoptin and exerts tumor-preferential cell killing. Danen-van Oorschot, A.A., Voskamp, P., Seelen, M.C., van Miltenburg, M.H., Bolk, M.W., Tait, S.W., Boesen-de Cock, J.G., Rohn, J.L., Borst, J., Noteborn, M.H. Cell Death Differ. (2004) [Pubmed]
  18. Repeat exposure to incremental doses of acetaminophen provides protection against acetaminophen-induced lethality in mice: an explanation for high acetaminophen dosage in humans without hepatic injury. Shayiq, R.M., Roberts, D.W., Rothstein, K., Snawder, J.E., Benson, W., Ma, X., Black, M. Hepatology (1999) [Pubmed]
  19. YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP transcription factors. Sawa, C., Yoshikawa, T., Matsuda-Suzuki, F., Deléhouzée, S., Goto, M., Watanabe, H., Sawada, J., Kataoka, K., Handa, H. J. Biol. Chem. (2002) [Pubmed]
  20. Abnormal PcG protein expression in Hodgkin's lymphoma. Relation with E2F6 and NFkappaB transcription factors. Sánchez-Beato, M., Sánchez, E., García, J.F., Pérez-Rosado, A., Montoya, M.C., Fraga, M., Artiga, M.J., Navarrete, M., Abraira, V., Morente, M., Esteller, M., Koseki, H., Vidal, M., Piris, M.A. J. Pathol. (2004) [Pubmed]
  21. The death effector domain-associated factor plays distinct regulatory roles in the nucleus and cytoplasm. Zheng, L., Schickling, O., Peter, M.E., Lenardo, M.J. J. Biol. Chem. (2001) [Pubmed]
  22. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Zimmerman, H.J., Maddrey, W.C. Hepatology (1995) [Pubmed]
  23. The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex. Trimarchi, J.M., Fairchild, B., Wen, J., Lees, J.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  24. Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function. Schlisio, S., Halperin, T., Vidal, M., Nevins, J.R. EMBO J. (2002) [Pubmed]
  25. The combination of ibuprofen and oxycodone/acetaminophen in the management of chronic cancer pain. Stambaugh, J.E., Drew, J. Clin. Pharmacol. Ther. (1988) [Pubmed]
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