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Gene Review

TUBA1A  -  tubulin, alpha 1a

Homo sapiens

Synonyms: Alpha-tubulin 3, B-ALPHA-1, FLJ25113, LIS3, TUBA3, ...
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Disease relevance of TUBA1A


High impact information on TUBA1A

  • We identified two patients with de novo mutations in TUBA3, the human homolog of Tuba1 [6].
  • A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes [7].
  • SUMO4 conjugates to I kappa B alpha and negatively regulates NF kappa B transcriptional activity [7].
  • UEV/Ubc complexes have been implicated in the assembly of Lys63-linked polyubiquitin chains that act as a novel signal in postreplicative DNA repair and I kappa B alpha kinase activation [8].
  • Reoxygenation of hypoxic cells appeared as a physiological effector of I kappa B-alpha tyrosine phosphorylation [9].

Chemical compound and disease context of TUBA1A


Biological context of TUBA1A


Anatomical context of TUBA1A

  • Pervanadate-induced I kappa B-alpha phosphorylation and NF-kappa B activation required expression of the T cell tyrosine kinase p56ick [9].
  • We have purified I kappa B-alpha, a major form of I kappa B with an apparent molecular size of 37 kd, from cytosol of human placenta [15].
  • A complementary DNA that corrects the radiation sensitivity and DNA synthesis defects in fibroblasts from an AT group D patient was isolated by expression cloning and shown to encode a truncated form of I kappa B-alpha, an inhibitor of the nuclear factor kappa B (NF-kappa B) transcriptional activator [2].
  • Newborn mice with a ubiquitous deletion of I kappa B alpha develop a severe hematological disorder characterized by an increase of granulocyte/erythroid/monocyte/macrophage colony-forming units (CFU-GEMM) and hypergranulopoiesis [17].
  • In contrast, in mice with a conditional deletion of I kappa B alpha only in the myeloid lineage (ikba(flox/flox) x LysM-Cre) and in fetal liver cell chimeras (ikba(FL delta/FL delta)), a cell-autonomous induction of the myeloproliferative disease was not observed [17].

Associations of TUBA1A with chemical compounds


Physical interactions of TUBA1A

  • Respiratory syncytial virus-induced RANTES production from human bronchial epithelial cells is dependent on nuclear factor-kappa B nuclear binding and is inhibited by adenovirus-mediated expression of inhibitor of kappa B alpha [21].
  • Mechanistic studies revealed that triptolide markedly decreased IL-1beta -induced NF-kappa B DNA binding capacity and cytosolic amount of p-I kappa B-alpha [22].

Enzymatic interactions of TUBA1A

  • SCFHOS-ROC1 binds IKK beta-phosphorylated I kappa B alpha and catalyzes its ubiquitination in the presence of ubiquitin, E1, and Cdc34 [23].
  • GSHPx overexpression also abolished the TNF alpha-mediated transient accumulation of the acidic and highly phosphorylated I kappa B-alpha isoform [24].
  • Sequence analysis revealed that purified CKII and the kinase activity within cell extracts phosphorylated I kappa B alpha at its C terminus at S-283, S-288, S-293, and T-291 [25].
  • ATM gene product phosphorylates I kappa B-alpha [26].
  • SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4 [27].

Regulatory relationships of TUBA1A

  • A nuclear complex was induced in phorbol myristate acetate-treated Jurkat T cells which bound specifically to the kappa B site of the IL-8 promoter and was inhibited by addition of purified I kappa B alpha to the reaction mixture [28].
  • Celecoxib also inhibited the TNF-induced interaction of Akt with I kappa B alpha kinase (IKK) [29].
  • Immunodepletion of CKII from these extracts abrogated both the basal and enhanced HIV-induced degradation of I kappa B alpha [25].
  • Two of the inhibitor-of-apoptosis proteins were downregulated because of an increase in 'second mitochondrial activator of caspases/Direct inhibitor-of-apoptosis protein binding protein with low pI.' Decrease in nuclear factor kappa B and increase in inhibitor of nuclear factor kappa B alpha expression favored the process of apoptosis [30].
  • We show that of the two forms of I kappa B alpha recovered from stimulated cells in a complex with RelA and p50, only the newly phosphorylated form, pI kappa B alpha, is a substrate for an in vitro reconstituted ubiquitin-proteasome system [31].

Other interactions of TUBA1A

  • Mice lacking RelB or I kappa B alpha, as well as both mice and humans with heterozygous NEMO mutations, develop skin lesions [32].
  • In order to characterize the regulation of the gene encoding the I kappa B-alpha/MAD3 inhibitor of the transcription factor NF-kappa B, we have isolated a human genomic clone and sequenced the promoter of this gene [33].
  • This is explained at least in part by the long-term downregulation of I kappa B alpha following CD28 signalling as opposed to phorbol myristate acetate alone [34].
  • We tested whether BCL3 could overcome the cytoplasmic retention of p50 by I kappa B alpha [35].
  • Activation of IKK in FLS was accompanied by phosphorylation and degradation of endogenous I kappa B alpha as determined by Western blot analysis [36].

Analytical, diagnostic and therapeutic context of TUBA1A


  1. Enhanced translation of chimaeric messenger RNAs containing a plant viral untranslated leader sequence. Jobling, S.A., Gehrke, L. Nature (1987) [Pubmed]
  2. Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha. Jung, M., Zhang, Y., Lee, S., Dritschilo, A. Science (1995) [Pubmed]
  3. Inhibition of endothelial cell activation by adenovirus-mediated expression of I kappa B alpha, an inhibitor of the transcription factor NF-kappa B. Wrighton, C.J., Hofer-Warbinek, R., Moll, T., Eytner, R., Bach, F.H., de Martin, R. J. Exp. Med. (1996) [Pubmed]
  4. Regulation of human retroviral latency by the NF-kappa B/I kappa B family: inhibition of human immunodeficiency virus replication by I kappa B through a Rev-dependent mechanism. Wu, B.Y., Woffendin, C., Duckett, C.S., Ohno, T., Nabel, G.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. Constitutive NF-kappa B activity in neurons. Kaltschmidt, C., Kaltschmidt, B., Neumann, H., Wekerle, H., Baeuerle, P.A. Mol. Cell. Biol. (1994) [Pubmed]
  6. Mutations in alpha-Tubulin Cause Abnormal Neuronal Migration in Mice and Lissencephaly in Humans. Keays, D.A., Tian, G., Poirier, K., Huang, G.J., Siebold, C., Cleak, J., Oliver, P.L., Fray, M., Harvey, R.J., Moln??r, Z., Pi??on, M.C., Dear, N., Valdar, W., Brown, S.D., Davies, K.E., Rawlins, J.N., Cowan, N.J., Nolan, P., Chelly, J., Flint, J. Cell (2007) [Pubmed]
  7. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Guo, D., Li, M., Zhang, Y., Yang, P., Eckenrode, S., Hopkins, D., Zheng, W., Purohit, S., Podolsky, R.H., Muir, A., Wang, J., Dong, Z., Brusko, T., Atkinson, M., Pozzilli, P., Zeidler, A., Raffel, L.J., Jacob, C.O., Park, Y., Serrano-Rios, M., Larrad, M.T., Zhang, Z., Garchon, H.J., Bach, J.F., Rotter, J.I., She, J.X., Wang, C.Y. Nat. Genet. (2004) [Pubmed]
  8. Molecular insights into polyubiquitin chain assembly: crystal structure of the Mms2/Ubc13 heterodimer. VanDemark, A.P., Hofmann, R.M., Tsui, C., Pickart, C.M., Wolberger, C. Cell (2001) [Pubmed]
  9. Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha. Imbert, V., Rupec, R.A., Livolsi, A., Pahl, H.L., Traenckner, E.B., Mueller-Dieckmann, C., Farahifar, D., Rossi, B., Auberger, P., Baeuerle, P.A., Peyron, J.F. Cell (1996) [Pubmed]
  10. Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Koong, A.C., Chen, E.Y., Giaccia, A.J. Cancer Res. (1994) [Pubmed]
  11. The NF-kappa B cascade is important in Bcl-xL expression and for the anti-apoptotic effects of the CD28 receptor in primary human CD4+ lymphocytes. Khoshnan, A., Tindell, C., Laux, I., Bae, D., Bennett, B., Nel, A.E. J. Immunol. (2000) [Pubmed]
  12. Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication. Beauparlant, P., Kwon, H., Clarke, M., Lin, R., Sonenberg, N., Wainberg, M., Hiscott, J. J. Virol. (1996) [Pubmed]
  13. Genistein reduces NF-kappa B in T lymphoma cells via a caspase-mediated cleavage of I kappa B alpha. Baxa, D.M., Yoshimura, F.K. Biochem. Pharmacol. (2003) [Pubmed]
  14. Identification of a novel blocker of I kappa B alpha kinase that enhances cellular apoptosis and inhibits cellular invasion through suppression of NF-kappa B-regulated gene products. Ichikawa, H., Takada, Y., Murakami, A., Aggarwal, B.B. J. Immunol. (2005) [Pubmed]
  15. Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA. Zabel, U., Baeuerle, P.A. Cell (1990) [Pubmed]
  16. Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Scheinman, R.I., Cogswell, P.C., Lofquist, A.K., Baldwin, A.S. Science (1995) [Pubmed]
  17. Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha. Rupec, R.A., Jundt, F., Rebholz, B., Eckelt, B., Weindl, G., Herzinger, T., Flaig, M.J., Moosmann, S., Plewig, G., Dörken, B., Förster, I., Huss, R., Pfeffer, K. Immunity (2005) [Pubmed]
  18. Tumor necrosis factor alpha-induced phosphorylation of I kappa B alpha is a signal for its degradation but not dissociation from NF-kappa B. Miyamoto, S., Maki, M., Schmitt, M.J., Hatanaka, M., Verma, I.M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  19. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Scherer, D.C., Brockman, J.A., Chen, Z., Maniatis, T., Ballard, D.W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  20. Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Sakamoto, K.M., Kim, K.B., Kumagai, A., Mercurio, F., Crews, C.M., Deshaies, R.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  21. Respiratory syncytial virus-induced RANTES production from human bronchial epithelial cells is dependent on nuclear factor-kappa B nuclear binding and is inhibited by adenovirus-mediated expression of inhibitor of kappa B alpha. Thomas, L.H., Friedland, J.S., Sharland, M., Becker, S. J. Immunol. (1998) [Pubmed]
  22. Triptolide suppresses IL-1beta-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts. Tao, Q.S., Ren, J.A., Li, J.S. Acta Pharmacol. Sin. (2007) [Pubmed]
  23. Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha. Tan, P., Fuchs, S.Y., Chen, A., Wu, K., Gomez, C., Ronai, Z., Pan, Z.Q. Mol. Cell (1999) [Pubmed]
  24. Inhibition of I kappa B-alpha phosphorylation and degradation and subsequent NF-kappa B activation by glutathione peroxidase overexpression. Kretz-Remy, C., Mehlen, P., Mirault, M.E., Arrigo, A.P. J. Cell Biol. (1996) [Pubmed]
  25. Casein kinase II phosphorylates I kappa B alpha at S-283, S-289, S-293, and T-291 and is required for its degradation. McElhinny, J.A., Trushin, S.A., Bren, G.D., Chester, N., Paya, C.V. Mol. Cell. Biol. (1996) [Pubmed]
  26. ATM gene product phosphorylates I kappa B-alpha. Jung, M., Kondratyev, A., Lee, S.A., Dimtchev, A., Dritschilo, A. Cancer Res. (1997) [Pubmed]
  27. SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4. Strack, P., Caligiuri, M., Pelletier, M., Boisclair, M., Theodoras, A., Beer-Romero, P., Glass, S., Parsons, T., Copeland, R.A., Auger, K.R., Benfield, P., Brizuela, L., Rolfe, M. Oncogene (2000) [Pubmed]
  28. NF-kappa B subunit-specific regulation of the interleukin-8 promoter. Kunsch, C., Rosen, C.A. Mol. Cell. Biol. (1993) [Pubmed]
  29. Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-kappa B activation through inhibition of activation of I kappa B alpha kinase and Akt in human non-small cell lung carcinoma: correlation with suppression of COX-2 synthesis. Shishodia, S., Koul, D., Aggarwal, B.B. J. Immunol. (2004) [Pubmed]
  30. Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Karmakar, S., Weinberg, M.S., Banik, N.L., Patel, S.J., Ray, S.K. Neuroscience (2006) [Pubmed]
  31. Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway. Alkalay, I., Yaron, A., Hatzubai, A., Orian, A., Ciechanover, A., Ben-Neriah, Y. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  32. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Pasparakis, M., Courtois, G., Hafner, M., Schmidt-Supprian, M., Nenci, A., Toksoy, A., Krampert, M., Goebeler, M., Gillitzer, R., Israel, A., Krieg, T., Rajewsky, K., Haase, I. Nature (2002) [Pubmed]
  33. Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF-kappa B: positive regulation by members of the rel/NF-kappa B family. Le Bail, O., Schmidt-Ullrich, R., Israël, A. EMBO J. (1993) [Pubmed]
  34. Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells. Bryan, R.G., Li, Y., Lai, J.H., Van, M., Rice, N.R., Rich, R.R., Tan, T.H. Mol. Cell. Biol. (1994) [Pubmed]
  35. BCL3 encodes a nuclear protein which can alter the subcellular location of NF-kappa B proteins. Zhang, Q., Didonato, J.A., Karin, M., McKeithan, T.W. Mol. Cell. Biol. (1994) [Pubmed]
  36. NF-kappa B regulation by I kappa B kinase in primary fibroblast-like synoviocytes. Aupperle, K.R., Bennett, B.L., Boyle, D.L., Tak, P.P., Manning, A.M., Firestein, G.S. J. Immunol. (1999) [Pubmed]
  37. Expression of a constitutive NF-kappa B-like activity is essential for proliferation of cultured bovine vascular smooth muscle cells. Bellas, R.E., Lee, J.S., Sonenshein, G.E. J. Clin. Invest. (1995) [Pubmed]
  38. Characterization of CD40 signaling determinants regulating nuclear factor-kappa B activation in B lymphocytes. Hsing, Y., Hostager, B.S., Bishop, G.A. J. Immunol. (1997) [Pubmed]
  39. Inhibition of the NF-kappa B transcription factor increases Bax expression in cancer cell lines. Bentires-Alj, M., Dejardin, E., Viatour, P., Van Lint, C., Froesch, B., Reed, J.C., Merville, M.P., Bours, V. Oncogene (2001) [Pubmed]
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