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Gene Review

KLHL2  -  kelch-like family member 2

Homo sapiens

Synonyms: ABP-KELCH, Actin-binding protein Mayven, Kelch-like protein 2, MAV, MAYVEN
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Disease relevance of KLHL2


High impact information on KLHL2

  • In primary rat hippocampal neurons, Mayven is highly expressed in the cell body and in neurite processes [1].
  • Somatic cell-hybrid analysis indicated that the human Mayven gene is located on chromosome 4q21.2, whereas the murine homolog gene is located on chromosome 8 [1].
  • Mayven induces c-Jun expression and cyclin D1 activation in breast cancer cells [2].
  • Overexpression of Mayven resulted in an induction of c-Jun protein levels, as well as increased AP-1 (activating protein 1) transcriptional activity in MCF-7 and T47D breast cancer cells through its BTB/POZ domain [2].
  • Mayven is a member of the kelch-related superfamily of proteins, characterized by a series of 'kelch' repeats at their carboxyl terminus and a BTB/POZ domain at their NH2-terminus [2].

Chemical compound and disease context of KLHL2

  • Thirty-seven patients with disseminated breast cancer refractory to previous therapy were treated with a combination of mitomycin, doxorubicin, and vinblastine (MAV) [6].

Biological context of KLHL2

  • In normal subjects, MAVP rapidly declined by 45 mmHg and FABF correspondingly increased 5.3-fold without a systemic pressor response during 10 s of light upright exercise at 5 W. Approximately 67% of the blood flow response was attributed to the venous pressure drop-dependent mechanism [7].
  • METHODS Cellular sequences localized next to MAV-integration sites in the tumor DNAs were used to screen a Bacterial Artificial Chromosomes (BACs) library and isolate BACs containing about 150 kilobases of normal DNA corresponding to MAV integration regions (MIRs) [8].
  • This study reinforces our previous conclusions that the MAV-induced nephroblastoma constitutes an excellent model in which to characterize new potential oncogenes and tumor suppressors involved in the establishment and maintenance of tumors [8].

Anatomical context of KLHL2

  • Here, we report that Mayven expression was abundant and diffuse in primary human epithelial breast tumor cells as compared to normal breast epithelial cells, where Mayven was detected in the normal breast layer of the mammary ducts [2].
  • Mayven also binds actin, and is involved in the cytoskeletal reorganization in oligodendrocyte precursor cells (O-2A cells) that leads to process elongation [9].
  • CONCLUSIONS: The MAV of dynamic CT may be a predictor of tumor angiogenesis in patients with lung carcinoma and lymph node involvement [10].
  • Results: With rapid pacing, there was an immediate shortening of the effective refractory period (ERP) and decreases in the transmitral atrial wave velocity (MAV) and the left atrial appendage emptying velocity (LAAV) [11].

Associations of KLHL2 with chemical compounds

  • DESIGN AND METHODS: In a multicenter trial 33 patients aged 61-65 years with de novo or secondary AML were treated with double induction therapy including high dose mitoxantrone, etoposide and ara-C (MAV) in the first course and m-amsacrine together with high dose ara-C (MAMAC) in the second course [5].
  • 12 patients were treated with an OPAL-derived regimen, 4 with the MAV regimen, 1 with vincristine and prednisone, 1 with 6-mercaptopurine [12].
  • This study indicates that the MAV combination is no better than doxorubicin given as a single agent [6].
  • The regimen consisted of mitoxantrone (M) 10 mg/m2 i.v. days 4-8, cytosine arabinoside (A) 100 mg/m2 continuous infusion days 1-8, and etoposide (VP-16) (V) 100-120 mg/m2 i.v. days 4-8 (MAV protocol) for relapsed and refractory AML [13].
  • Except MAV 3 all Rps. viridis mutants are different from those selected by their resistance towards the closely related triazine terbutryn [14].

Physical interactions of KLHL2


Analytical, diagnostic and therapeutic context of KLHL2

  • Binding assays and far Western blotting analysis demonstrated association of Mayven with actin [1].
  • Mayven overexpression resulted in an increase in the process outgrowth of O-2A cells and in the lengths of the processes, while microinjection of Mayven-specific antibodies inhibited process extension in these cells [9].
  • Whole-cell DNAs of 14 reference species were extracted and amplified by PCR with the MYCOB, MAV, and MIN primers [15].
  • We conclude that MAV therapy is a highly active antileukemic combination with acceptable toxicity, which is recommended for further clinical trials in untreated AML [13].


  1. Characterization of Mayven, a novel actin-binding protein predominantly expressed in brain. Soltysik-Espanola, M., Rogers, R.A., Jiang, S., Kim, T.A., Gaedigk, R., White, R.A., Avraham, H., Avraham, S. Mol. Biol. Cell (1999) [Pubmed]
  2. Mayven induces c-Jun expression and cyclin D1 activation in breast cancer cells. Bu, X., Avraham, H.K., Li, X., Lim, B., Jiang, S., Fu, Y., Pestell, R.G., Avraham, S. Oncogene (2005) [Pubmed]
  3. Characterization of avian myeloblastosis-associated virus DNA intermediates. Bergmann, D.G., Souza, L.M., Baluda, M.A. J. Virol. (1980) [Pubmed]
  4. Deletions within the U3 long terminal repeat alter the tumorigenic potential of myeloblastosis associated virus type 1(N). Khelifi-Younes, C., Dambrine, G., Cherel, Y., Soubieux, D., Li, C.L., Perbal, B. Virology (2003) [Pubmed]
  5. Intensified double induction therapy with high dose mitoxantrone, etoposide, m-amsacrine and high dose ara-C for elderly acute myeloid leukemia patients aged 61-65 years. Schaich, M., Illmer, T., Aulitzky, W., Bodenstein, H., Clemens, M., Neubauer, A., Repp, R., Schäkel, U., Soucek, S., Wandt, H., Ehninger, G. Haematologica (2002) [Pubmed]
  6. Mitomycin, doxorubicin, and vinblastine as second-line chemotherapy in patients with advanced breast cancer. Borovik, R., Epelbaum, R., Cohen, Y., Robinson, E. Cancer treatment reports. (1986) [Pubmed]
  7. Muscle pump-dependent self-perfusion mechanism in legs in normal subjects and patients with heart failure. Shiotani, I., Sato, H., Sato, H., Yokoyama, H., Ohnishi, Y., Hishida, E., Kinjo, K., Nakatani, D., Kuzuya, T., Hori, M. J. Appl. Physiol. (2002) [Pubmed]
  8. Integration of Myeloblastosis Associated Virus proviral sequences occurs in the vicinity of genes encoding signaling proteins and regulators of cell proliferation. Li, C.L., Coullin, P., Bernheim, A., Joliot, V., Auffray, C., Zoroob, R., Perbal, B. Cell Commun. Signal (2006) [Pubmed]
  9. Process elongation of oligodendrocytes is promoted by the Kelch-related actin-binding protein Mayven. Jiang, S., Avraham, H.K., Park, S.Y., Kim, T.A., Bu, X., Seng, S., Avraham, S. J. Neurochem. (2005) [Pubmed]
  10. Contrast-enhanced dynamic computed tomography for the evaluation of tumor angiogenesis in patients with lung carcinoma. Tateishi, U., Kusumoto, M., Nishihara, H., Nagashima, K., Morikawa, T., Moriyama, N. Cancer (2002) [Pubmed]
  11. Temporal patterns of progression and regression of electrical and mechanical remodeling of the atrium. Kinebuchi, O., Mitamura, H., Shiroshita-Takeshita, A., Kurita, Y., Ohashi, N., Tanimoto, K., Fukuda, Y., Ieda, M., Sato, T., Hara, M., Takatsuki, S., Ogawa, S. International journal of cardiology. (2005) [Pubmed]
  12. Acute lymphoblastic leukemia in the elderly. Delannoy, A., Ferrant, A., Bosly, A., Chatelain, C., Doyen, C., Martiat, P., Michaux, J.L., Sokal, G. Eur. J. Haematol. (1990) [Pubmed]
  13. Mitoxantrone, cytosine arabinoside, and VP-16 in 36 patients with relapsed and refractory acute myeloid leukemia. Link, H., Freund, M., Diedrich, H., Wilke, H., Austein, J., Henke, M., Wandt, H., Fackler-Schwalbe, E., Schlimok, G., Hoffmann, R. Haematology and blood transfusion. (1990) [Pubmed]
  14. Sequence analysis of four atrazine-resistant mutants from Rhodopseudomonas viridis. Ewald, G., Wiessner, C., Michel, H. Z. Naturforsch., C, J. Biosci. (1990) [Pubmed]
  15. Identification and differentiation of Mycobacterium avium and M. intracellulare by PCR. Chen, Z.H., Butler, W.R., Baumstark, B.R., Ahearn, D.G. J. Clin. Microbiol. (1996) [Pubmed]
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