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Gene Review

TNFSF12  -  tumor necrosis factor (ligand) superfamily...

Homo sapiens

Synonyms: APO3 ligand, APO3L, DR3LG, TNF-related weak inducer of apoptosis, TWEAK, ...
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Disease relevance of TNFSF12


Psychiatry related information on TNFSF12

  • DATA SOURCES: We searched MEDLINE from 1966 to July 1997 for alcoholism or alcohol-drinking and for CAGE, AUDIT, BMAST, TWEAK, T-ACE, MAST, SMAST, or SAAST; Citations Indexes for newer screening questionnaires and those without acronyms; and MEDLINE from 1996 to July 1997 for alcoholism or alcohol-drinking and screening [6].
  • The TWEAK and Alcohol Use Disorders Identification Test (AUDIT) questionnaires had high AUROCs (0.87-0.93) for past-year alcohol abuse or dependence in black or white women, but had sensitivities less than 80% at traditional cut points [6].
  • TWEAK is an acronym for Tolerance (T1 number of drinks to feel high; T2, number of drinks one can hold), Worry about drinking, Eye-opener (morning drinking), Amnesia (blackouts), and Cut down on drinking (K/C) [7].
  • Assessing alcohol misuse during pregnancy: evaluating psychometric properties of the CAGE, T-ACE and TWEAK in a Brazilian setting [8].
  • Measures of provider advice on alcohol consumption, demographic characteristics, caffeine intake, smoking, other drug use, alcohol risk (using the TWEAK scale), and depressive symptoms on the Center for Epidemiological Studies Depression Scale (CES-D) were collected [9].

High impact information on TNFSF12

  • Five different assays demonstrate TWEAK-TweakR binding, and the interaction affinity constant (Kd) is within a physiologically relevant range of 2.3 +/- 0.1 nM [10].
  • These results revealed a novel pathway of monocyte cytotoxicity against tumor cells that is mediated by TWEAK and potentiated by IFN-gamma [11].
  • Although freshly isolated PBMCs expressed no detectable level of TWEAK on their surfaces, a remarkable TWEAK expression was rapidly observed on monocytes upon stimulation with interferon (IFN)-gamma but not with IFN-alpha or lipopolysaccharide [11].
  • TWEAK, a new member of the tumor necrosis factor (TNF) family, induces cell death in some tumor cell lines, but its physiological functions are largely unknown [11].
  • Involvement of TWEAK in interferon gamma-stimulated monocyte cytotoxicity [11].

Chemical compound and disease context of TNFSF12

  • Screening measures included questions about cigarettes; questions from the Alcohol Use Disorders Identification Test about consumption (hazardous drinking); the TWEAK test (problem drinking); a drug abuse screen; the Patient Health Questionnaire (psychiatric conditions); and the PTSD (posttraumatic stress disorder) Checklist [12].

Biological context of TNFSF12


Anatomical context of TNFSF12

  • Further studies demonstrated that AE7, a cloned Th1 line, and splenic T cells express TWEAK, TRAIL, and Fas ligand, and inhibiting these molecules also inhibited macrophage killing [13].
  • In this study, we characterized the TWEAK-induced cell death in several tumor cell lines that exhibited distinct features [14].
  • Although a pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, inhibited the TWEAK-induced cell death in HSC3 cells, it rather sensitized HT-29 cells to TWEAK-induced cell death by necrosis [14].
  • During the process of TWEAK-induced necrosis, cathepsin B was released from lysosome to cytosol [14].
  • Primary cultured normal human keratinocytes constitutively expressed a TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), and produced regulated on activation, normal T expressed and secreted (RANTES) upon TWEAK stimulation in a concentration-dependent manner [15].

Associations of TNFSF12 with chemical compounds


Physical interactions of TNFSF12


Regulatory relationships of TNFSF12

  • The TWEAK-induced RANTES production was abrogated by anti-Fn14 antibody, and synergistically augmented by simultaneous stimulation with transforming growth factor-beta [15].
  • On the other hand, the TWEAK-induced VCAM-1 expression was inhibited by TGF-beta1 [2].
  • The ICAM-1 expression induced by TWEAK was augmented by TGF-beta1 [2].
  • TWEAK-induced activation of MMP-9 was mediated by activation of NF-kappaB [3].
  • These results suggest that TWEAK is involved in atherosclerosis by inducing pro-inflammatory cytokines and extracellular matrix degrading enzymes, which reduce plaque stability [3].

Other interactions of TNFSF12


Analytical, diagnostic and therapeutic context of TNFSF12


  1. TWEAK stimulation of astrocytes and the proinflammatory consequences. Saas, P., Boucraut, J., Walker, P.R., Quiquerez, A.L., Billot, M., Desplat-Jego, S., Chicheportiche, Y., Dietrich, P.Y. Glia (2000) [Pubmed]
  2. Proinflammatory effects of tumour necrosis factor-like weak inducer of apoptosis (TWEAK) on human gingival fibroblasts. Hosokawa, Y., Hosokawa, I., Ozaki, K., Nakae, H., Matsuo, T. Clin. Exp. Immunol. (2006) [Pubmed]
  3. TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages. Kim, S.H., Kang, Y.J., Kim, W.J., Woo, D.K., Lee, Y., Kim, D.I., Park, Y.B., Kwon, B.S., Park, J.E., Lee, W.H. Circ. J. (2004) [Pubmed]
  4. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)-fibroblast growth factor-inducible 14 (Fn14) signaling system regulates glioma cell survival via NFkappaB pathway activation and BCL-XL/BCL-W expression. Tran, N.L., McDonough, W.S., Savitch, B.A., Sawyer, T.F., Winkles, J.A., Berens, M.E. J. Biol. Chem. (2005) [Pubmed]
  5. The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells. Kaplan, M.J., Lewis, E.E., Shelden, E.A., Somers, E., Pavlic, R., McCune, W.J., Richardson, B.C. J. Immunol. (2002) [Pubmed]
  6. Alcohol screening questionnaires in women: a critical review. Bradley, K.A., Boyd-Wickizer, J., Powell, S.H., Burman, M.L. JAMA (1998) [Pubmed]
  7. Use of the TWEAK test in screening for alcoholism/heavy drinking in three populations. Chan, A.W., Pristach, E.A., Welte, J.W., Russell, M. Alcohol. Clin. Exp. Res. (1993) [Pubmed]
  8. Assessing alcohol misuse during pregnancy: evaluating psychometric properties of the CAGE, T-ACE and TWEAK in a Brazilian setting. Moraes, C.L., Viellas, E.F., Reichenheim, M.E. J. Stud. Alcohol (2005) [Pubmed]
  9. Health care provider advice and risk factors associated with alcohol consumption following pregnancy recognition. O'Connor, M.J., Whaley, S.E. J. Stud. Alcohol (2006) [Pubmed]
  10. A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Wiley, S.R., Cassiano, L., Lofton, T., Davis-Smith, T., Winkles, J.A., Lindner, V., Liu, H., Daniel, T.O., Smith, C.A., Fanslow, W.C. Immunity (2001) [Pubmed]
  11. Involvement of TWEAK in interferon gamma-stimulated monocyte cytotoxicity. Nakayama, M., Kayagaki, N., Yamaguchi, N., Okumura, K., Yagita, H. J. Exp. Med. (2000) [Pubmed]
  12. Screening for substance abuse and psychiatric disorders among women patients in a VA Health Care System. Davis, T.M., Bush, K.R., Kivlahan, D.R., Dobie, D.J., Bradley, K.A. Psychiatric services (Washington, D.C.) (2003) [Pubmed]
  13. TRAIL (Apo2 ligand) and TWEAK (Apo3 ligand) mediate CD4+ T cell killing of antigen-presenting macrophages. Kaplan, M.J., Ray, D., Mo, R.R., Yung, R.L., Richardson, B.C. J. Immunol. (2000) [Pubmed]
  14. Multiple pathways of TWEAK-induced cell death. Nakayama, M., Ishidoh, K., Kayagaki, N., Kojima, Y., Yamaguchi, N., Nakano, H., Kominami, E., Okumura, K., Yagita, H. J. Immunol. (2002) [Pubmed]
  15. Induction of RANTES by TWEAK/Fn14 interaction in human keratinocytes. Jin, L., Nakao, A., Nakayama, M., Yamaguchi, N., Kojima, Y., Nakano, N., Tsuboi, R., Okumura, K., Yagita, H., Ogawa, H. J. Invest. Dermatol. (2004) [Pubmed]
  16. TWEAK is a novel arthritogenic mediator. Perper, S.J., Browning, B., Burkly, L.C., Weng, S., Gao, C., Giza, K., Su, L., Tarilonte, L., Crowell, T., Rajman, L., Runkel, L., Scott, M., Atkins, G.J., Findlay, D.M., Zheng, T.S., Hess, H. J. Immunol. (2006) [Pubmed]
  17. Receptor activator of nuclear factor kappaB ligand plays a nonredundant role in doxorubicin-induced apoptosis. Müller, I., Pfister, S.M., Grohs, U., Zweigner, J., Handgretinger, R., Niethammer, D., Bruchelt, G. Cancer Res. (2003) [Pubmed]
  18. Functional expression of TWEAK in human colonic adenocarcinoma cells. Kawakita, T., Shiraki, K., Yamanaka, Y., Yamaguchi, Y., Saitou, Y., Enokimura, N., Yamamoto, N., Okano, H., Sugimoto, K., Murata, K., Nakano, T. Int. J. Oncol. (2005) [Pubmed]
  19. Self-report screening tests for alcohol problems in primary care. Allen, J.P., Maisto, S.A., Connors, G.J. Arch. Intern. Med. (1995) [Pubmed]
  20. Fn14 is upregulated in cytokine-stimulated vascular smooth muscle cells and is expressed in human carotid atherosclerotic plaques: modulation by atorvastatin. Muñoz-García, B., Martín-Ventura, J.L., Martínez, E., Sánchez, S., Hernández, G., Ortega, L., Ortiz, A., Egido, J., Blanco-Colio, L.M. Stroke (2006) [Pubmed]
  21. Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3). Kaptein, A., Jansen, M., Dilaver, G., Kitson, J., Dash, L., Wang, E., Owen, M.J., Bodmer, J.L., Tschopp, J., Farrow, S.N. FEBS Lett. (2000) [Pubmed]
  22. TWEAK and Fn14: New molecular targets for cancer therapy? Winkles, J.A., Tran, N.L., Berens, M.E. Cancer Lett. (2006) [Pubmed]
  23. A previously unrecognized protein-protein interaction between TWEAK and CD163: potential biological implications. Bover, L.C., Cardó-Vila, M., Kuniyasu, A., Sun, J., Rangel, R., Takeya, M., Aggarwal, B.B., Arap, W., Pasqualini, R. J. Immunol. (2007) [Pubmed]
  24. Dual role for TWEAK in angiogenic regulation. Jakubowski, A., Browning, B., Lukashev, M., Sizing, I., Thompson, J.S., Benjamin, C.D., Hsu, Y.M., Ambrose, C., Zheng, T.S., Burkly, L.C. J. Cell. Sci. (2002) [Pubmed]
  25. An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein. Pradet-Balade, B., Medema, J.P., López-Fraga, M., Lozano, J.C., Kolfschoten, G.M., Picard, A., Martínez-A, C., Garcia-Sanz, J.A., Hahne, M. EMBO J. (2002) [Pubmed]
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