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Gene Review

MAP4  -  microtubule-associated protein 4

Homo sapiens

Synonyms: MAP-4, Microtubule-associated protein 4
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Disease relevance of MAP4

  • Adenovirus 2 E1B-55K protein relieves p53-mediated transcriptional repression of the survivin and MAP4 promoters [1].
  • These techniques have revealed that thin processes extending from monkey kidney cells (TC-7), and those made by human neuroblastoma cells (IMR-32) in response to retinoic acid, are often deficient in MAP4 immunoreactivity [2].
  • We reported that wild-type p53 induction by doxorubicin in C127 breast cancer cells repressed MAP4, decreased microtubule polymerization, and increased Vinca alkaloid sensitivity [3].
  • The COOH-terminal MT binding domain of MAP4 was expressed in Escherichia coli as a glutathione transferase fusion protein and was injected into rabbits to produce an antiserum that was then affinity purified and shown to be monospecific for MAP4 [4].
  • To address the significance of beta-tubulin and MAP4 alterations in childhood ALL, two CCRF-CEM-derived Vinca alkaloid resistant cell lines, VCR R (vincristine) and VLB100 (vinblastine), were examined [5].

Psychiatry related information on MAP4


High impact information on MAP4

  • However, MAP-2, MAP-4, and tau have common repetitive microtubule-binding motifs [6].
  • We report that trichostatin A (TSA), an inhibitor of histone deacetylases (HDACs), abrogates the ability of p53 to repress the transcription of two genes that it negatively regulates, Map4 and stathmin [7].
  • Stabilizing factors include a large group of microtubule-associated proteins (MAPs; e.g. MAP4, XMAP215, XMAP230/XMAP4 and XMAP310) and the destabilizing factors are a growing family of proteins (e.g. Stathmin/Op18 and XKCM1) [8].
  • Removal of MAP4 from microtubules in vivo produces no observable phenotype at the cellular level [4].
  • Cells progressed to mitosis with morphologically normal spindles in the absence of MAP4 binding to MTs [4].

Biological context of MAP4

  • Finally, we tested the effects of MAP4 phosphorylation on microtubule dynamics [9].
  • Moreover, septin depletion increased the number of cells with abnormal nuclei, and this effect was blocked by gene silencing of MAP4 [10].
  • This approach relies on the finding that overexpression of MAP4 alone stabilizes microtubules during all phases of the cell cycle in human leukemia cells, and causes a potent mitotic block and a dramatic, previously unobserved, phenotype characterized by large monoastral spindles [11].
  • Interestingly, the tubulin-sequestering derivative suppressed the monoastral mitotic phenotype of MAP4 (i.e. coexpression facilitated the formation of functional spindles) [11].
  • Evidence that pMAP4.245 encodes MAP4 sequences includes immunoabsorption of MAP4 antibodies with the pMAP4.245 fusion protein, as well as identity of protein sequences obtained from HeLa 210 kD MAP4 with amino acid sequences encoded by pMAP4.245 [12].

Anatomical context of MAP4

  • In this study, we have investigated the mechanism by which p34cdc2 kinase associates with the microtubule cytoskeleton in primate tissue culture cells whose major MAP is known to be MAP4 [9].
  • A polyclonal antiserum raised against a HeLa cell microtubule-associated protein of Mr 210,000 (210 kD MAP or MAP4), an abundant non-neuronal MAP, was used to isolate cDNA clones encoding MAP4 from a human fetal brain lambda gt11 cDNA expression library [12].
  • Microtubule-associated protein 4 (MAP4) regulates assembly, protomer-polymer partitioning and synthesis of tubulin in cultured cells [13].
  • Similar multimeric tubulin-binding domains in other proteins of the MAP2 class, including tau in axons and MAP4 in glial cells, may play the same role in the development and support of asymmetric cell morphology [14].
  • To test the hypothesis that phosphorylation at these sites influences microtubule properties or cell cycle progression, we prepared stable cell lines that inducibly express versions of MAP4 in which phosphorylation of these two serines was prevented by their replacement with alanine, lysine, or glutamate residues (AA-, KK-, or EE-MAP4) [15].

Associations of MAP4 with chemical compounds


Physical interactions of MAP4

  • Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau [12].

Regulatory relationships of MAP4


Other interactions of MAP4

  • We now report that, as with MAP4 and tau, MAP2 isoforms containing four (4R) instead of three (3R) tandem repeats in their microtubule binding domains do exist in human and rat brain [18].
  • The association of p34cdc2/cyclin B kinase with microtubules was also shown biochemically to be mediated by MAP4 [9].
  • In contrast, however, the microtubule-stabilizing activity of MAP4 was found to suppress the activities of two distinct and specific catastrophe promoters, namely, XKCM1 and a nonsequestering truncation derivative of Op18/stathmin [19].
  • Cells containing mut-p53 displayed increased polymerisation of tubulin, increased protein levels of the class IV beta-tubulin isotype, STOP and survivin, and reduced protein levels of class II beta-tubulin isotype, MAP4 and FHIT [20].
  • In the previous paper (Ookata et al., (1997) Biochemistry, 36: 249-259), we identified two mitotic cdc2 kinase phosphorylation sites (Ser696 and Ser787) in the proline-rich region of human MAP4 [21].

Analytical, diagnostic and therapeutic context of MAP4


  1. Adenovirus 2 E1B-55K protein relieves p53-mediated transcriptional repression of the survivin and MAP4 promoters. Punga, T., Akusjärvi, G. FEBS Lett. (2003) [Pubmed]
  2. Cellular microtubules heterogeneous in their content of microtubule-associated protein 4 (MAP4). Chapin, S.J., Bulinski, J.C. Cell Motil. Cytoskeleton (1994) [Pubmed]
  3. A Phase I/pilot study of sequential doxorubicin/vinorelbine: effects on p53 and microtubule-associated protein 4. Bash-Babula, J., Toppmeyer, D., Labassi, M., Reidy, J., Orlick, M., Senzon, R., Alli, E., Kearney, T., August, D., Shih, W., Yang, J.M., Hait, W.N. Clin. Cancer Res. (2002) [Pubmed]
  4. Removal of MAP4 from microtubules in vivo produces no observable phenotype at the cellular level. Wang, X.M., Peloquin, J.G., Zhai, Y., Bulinski, J.C., Borisy, G.G. J. Cell Biol. (1996) [Pubmed]
  5. Multiple microtubule alterations are associated with Vinca alkaloid resistance in human leukemia cells. Kavallaris, M., Tait, A.S., Walsh, B.J., He, L., Horwitz, S.B., Norris, M.D., Haber, M. Cancer Res. (2001) [Pubmed]
  6. Role of microtubule-associated proteins in the control of microtubule assembly. Maccioni, R.B., Cambiazo, V. Physiol. Rev. (1995) [Pubmed]
  7. Transcriptional repression by wild-type p53 utilizes histone deacetylases, mediated by interaction with mSin3a. Murphy, M., Ahn, J., Walker, K.K., Hoffman, W.H., Evans, R.M., Levine, A.J., George, D.L. Genes Dev. (1999) [Pubmed]
  8. Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Andersen, S.S. Trends Cell Biol. (2000) [Pubmed]
  9. Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. Ookata, K., Hisanaga, S., Bulinski, J.C., Murofushi, H., Aizawa, H., Itoh, T.J., Hotani, H., Okumura, E., Tachibana, K., Kishimoto, T. J. Cell Biol. (1995) [Pubmed]
  10. Mammalian septins regulate microtubule stability through interaction with the microtubule-binding protein MAP4. Kremer, B.E., Haystead, T., Macara, I.G. Mol. Biol. Cell (2005) [Pubmed]
  11. Interphase and monoastral-mitotic phenotypes of overexpressed MAP4 are modulated by free tubulin concentrations. Holmfeldt, P., Brattsand, G., Gullberg, M. J. Cell. Sci. (2003) [Pubmed]
  12. Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau. Chapin, S.J., Bulinski, J.C. J. Cell. Sci. (1991) [Pubmed]
  13. Microtubule-associated protein 4 (MAP4) regulates assembly, protomer-polymer partitioning and synthesis of tubulin in cultured cells. Nguyen, H.L., Gruber, D., Bulinski, J.C. J. Cell. Sci. (1999) [Pubmed]
  14. Actin depolymerisation induces process formation on MAP2-transfected non-neuronal cells. Edson, K., Weisshaar, B., Matus, A. Development (1993) [Pubmed]
  15. Phosphorylation of MAP4 affects microtubule properties and cell cycle progression. Chang, W., Gruber, D., Chari, S., Kitazawa, H., Hamazumi, Y., Hisanaga, S., Bulinski, J.C. J. Cell. Sci. (2001) [Pubmed]
  16. Binding of JNK/SAPK to MEKK1 is regulated by phosphorylation. Gallagher, E.D., Xu, S., Moomaw, C., Slaughter, C.A., Cobb, M.H. J. Biol. Chem. (2002) [Pubmed]
  17. DNA damage increases sensitivity to vinca alkaloids and decreases sensitivity to taxanes through p53-dependent repression of microtubule-associated protein 4. Zhang, C.C., Yang, J.M., Bash-Babula, J., White, E., Murphy, M., Levine, A.J., Hait, W.N. Cancer Res. (1999) [Pubmed]
  18. Four repeat MAP2 isoforms in human and rat brain. Kindler, S., Garner, C.C. Brain Res. Mol. Brain Res. (1994) [Pubmed]
  19. MAP4 counteracts microtubule catastrophe promotion but not tubulin-sequestering activity in intact cells. Holmfeldt, P., Brattsand, G., Gullberg, M. Curr. Biol. (2002) [Pubmed]
  20. Drug resistance associated with loss of p53 involves extensive alterations in microtubule composition and dynamics. Galmarini, C.M., Kamath, K., Vanier-Viornery, A., Hervieu, V., Peiller, E., Falette, N., Puisieux, A., Ann Jordan, M., Dumontet, C. Br. J. Cancer (2003) [Pubmed]
  21. Serum-dependent phosphorylation of human MAP4 at Ser696 in cultured mammalian cells. Srsen, V., Kitazawa, H., Sugita, M., Murofushi, H., Bulinski, J.C., Kishimoto, T., Hisanaga, S. Cell Struct. Funct. (1999) [Pubmed]
  22. The projection domain of MAP4 suppresses the microtubule-bundling activity of the microtubule-binding domain. Iida, J., Itoh, T.J., Hotani, H., Nishiyama, K., Murofushi, H., Bulinski, J.C., Hisanaga, S. J. Mol. Biol. (2002) [Pubmed]
  23. Adenovirus-mediated p16 gene transfer changes the sensitivity to taxanes and Vinca alkaloids of human ovarian cancer cells. Kawakami, Y., Hama, S., Hiura, M., Nogawa, T., Chiba, T., Yokoyama, T., Takashima, S., Tajiri, H., Eguchi, K., Nagai, N., Shigemasa, K., Ohama, K., Kurisu, K., Heike, Y. Anticancer Res. (2001) [Pubmed]
  24. Chicken microtubule-associated protein 4 (MAP4): a novel member of the MAP4 family. Stassen, M.P., Thole, H.H., Schaaf, C., Marquart, A.U., Sinner, K., Gehrig, H. Histochem. Cell Biol. (1996) [Pubmed]
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