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Gene Review

BLMH  -  bleomycin hydrolase

Homo sapiens

Synonyms: BH, BLM hydrolase, BMH, Bleomycin hydrolase
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Disease relevance of BLMH


Psychiatry related information on BLMH


High impact information on BLMH

  • Bleomycin hydrolase is associated with risk of sporadic Alzheimer's disease [6].
  • The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase [7].
  • Benzhydrazone [BH; 1H-benz[f]indene-1,3(2H) -dionebis(amidinohydrazone)] significantly inhibits glycosylation of proteins, but only in cells infected with herpes simplex virus [8].
  • We report on a herpes simplex virus type 1 (HSV-1) mutant resistant to BH [8].
  • Intertypic recombinants were obtained which showed that BH resistance is encoded in the DNA of the mutant virus and may be transferred into the genome of BH-sensitive HSV [8].

Chemical compound and disease context of BLMH


Biological context of BLMH


Anatomical context of BLMH


Associations of BLMH with chemical compounds


Co-localisations of BLMH

  • We also found that hBH interacted and colocalized with APP as determined by subcellular fractionation, in vitro binding assay, and confocal immunolocalization [16].

Regulatory relationships of BLMH


Other interactions of BLMH

  • Our findings suggest a regulatory role for hBH in APP processing pathways [16].
  • To test this hypothesis, we examined this polymorphism in 621 rigorously evaluated patients and 502 control subjects (all caucasian) but were unable to detect an association between BH and AD even after controlling for age, gender, and apolipoprotein E (ApoE) genotype [4].
  • Cysteine 73 in bleomycin hydrolase is critical for amyloid precursor protein processing [18].
  • Consequently, TF-R showed decreased cellular accumulation and retention of BLM, increased BLM hydrolase activity and elevated DNA repair activity concomitant with increased poly(ADP-ribose) polymerase activity as compared with TF-S [20].

Analytical, diagnostic and therapeutic context of BLMH

  • Northern blot analysis of poly(A)+ RNAs isolated from a variety of human tissues demonstrated that human bleomycin hydrolase is expressed in all examined tissues, which is consistent with a putative role of this protein as a proteolytic enzyme involved in norman cellular protein degradation and turnover [2].
  • Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization [21].
  • We now demonstrate intrinsic endopeptidase activity associated with human BH (hBH) using artificial substrates and intracellular dimerization of hBH using a yeast two-hybrid assay [22].
  • The regional and cellular distribution of mRNA encoding hBH in the brain from controls and patients with AD was examined using in situ hybridization [23].
  • Treatment of mice bearing Daudi xenografts with an inhibitor of BLM hydrolase, L-trans-epoxysuccinyl-leucylamido-(4-guanidino)butane (E-64), prior to [3H]BLM A2 treatment did not affect the amount of BLM accumulated but inhibited BLM A2 metabolism in the xenografts [24].


  1. Genomic structure and genetic mapping of the human neutral cysteine protease bleomycin hydrolase. Montoya, S.E., Ferrell, R.E., Lazo, J.S. Cancer Res. (1997) [Pubmed]
  2. Cloning and expression analysis of human bleomycin hydrolase, a cysteine proteinase involved in chemotherapy resistance. Ferrando, A.A., Velasco, G., Campo, E., Lopez-Otin, C. Cancer Res. (1996) [Pubmed]
  3. Gene characterization, promoter analysis, and chromosomal localization of human bleomycin hydrolase. Ferrando, A.A., Pendás, A.M., Llano, E., Velasco, G., Lidereau, R., López-Otín, C. J. Biol. Chem. (1997) [Pubmed]
  4. Association between bleomycin hydrolase and Alzheimer's disease in caucasians. Farrer, L.A., Abraham, C.R., Haines, J.L., Rogaeva, E.A., Song, Y., McGraw, W.T., Brindle, N., Premkumar, S., Scott, W.K., Yamaoka, L.H., Saunders, A.M., Roses, A.D., Auerbach, S.A., Sorbi, S., Duara, R., Pericak-Vance, M.A., St George-Hyslop, P.H. Ann. Neurol. (1998) [Pubmed]
  5. Polymorphisms of the human apolipoprotein E promoter and bleomycin hydrolase gene: risk factors for Alzheimer's dementia? Thome, J., Gewirtz, J.C., Sakai, N., Zachariou, V., Retz-Junginger, P., Retz, W., Duman, R.S., Rösler, M. Neurosci. Lett. (1999) [Pubmed]
  6. Bleomycin hydrolase is associated with risk of sporadic Alzheimer's disease. Montoya, S.E., Aston, C.E., DeKosky, S.T., Kamboh, M.I., Lazo, J.S., Ferrell, R.E. Nat. Genet. (1998) [Pubmed]
  7. The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase. Zheng, W., Johnston, S.A., Joshua-Tor, L. Cell (1998) [Pubmed]
  8. Characterization of a herpes simplex virus type 1 mutant resistant to benzhydrazone, a selective inhibitor of herpesvirus glycosylation. Tognon, M., Manservigi, R., Cavrini, V., Campadelli-Fiume, G. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  9. Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase. Zimny, J., Sikora, M., Guranowski, A., Jakubowski, H. J. Biol. Chem. (2006) [Pubmed]
  10. Identification of duplicated genes in 17q11.2 using FISH on stretched chromosomes and DNA fibers. Bentivegna, A., Venturin, M., Gervasini, C., Corrado, L., Larizza, L., Riva, P. Hum. Genet. (2001) [Pubmed]
  11. Human bleomycin hydrolase binds ribosomal proteins. Koldamova, R.P., Lefterov, I.M., DiSabella, M.T., Almonte, C., Watkins, S.C., Lazo, J.S. Biochemistry (1999) [Pubmed]
  12. Characteristics of bleomycin-resistant phenotypes of human cell sublines and circumvention of bleomycin resistance by liblomycin. Lazo, J.S., Braun, I.D., Labaree, D.C., Schisselbauer, J.C., Meandzija, B., Newman, R.A., Kennedy, K.A. Cancer Res. (1989) [Pubmed]
  13. The C-terminus of human bleomycin hydrolase is required for protection against bleomycin-induced chromosomal damage. Lefterov, I.M., Koldamova, R.P., King, J., Lazo, J.S. Mutat. Res. (1998) [Pubmed]
  14. Bleomycin hydrolase immunoreactivity in senile plaque in the brains of patients with Alzheimer's disease. Namba, Y., Ouchi, Y., Takeda, A., Ueki, A., Ikeda, K. Brain Res. (1999) [Pubmed]
  15. Further characterization of bleomycin-resistant HeLa cells and analysis of resistance mechanism. Urade, M., Sugi, M., Matsuya, T. Jpn. J. Cancer Res. (1988) [Pubmed]
  16. Human bleomycin hydrolase regulates the secretion of amyloid precursor protein. Lefterov, I.M., Koldamova, R.P., Lazo, J.S. FASEB J. (2000) [Pubmed]
  17. An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9. Koldamova, R.P., Lefterov, I.M., DiSabella, M.T., Lazo, J.S. Mol. Pharmacol. (1998) [Pubmed]
  18. Cysteine 73 in bleomycin hydrolase is critical for amyloid precursor protein processing. Lefterov, I.M., Koldamova, R.P., Lefterova, M.I., Schwartz, D.R., Lazo, J.S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  19. Lidocaine potentiation of bleomycin A2 cytotoxicity and DNA strand breakage in L1210 and human A-253 cells. Lazo, J.S., Braun, I.D., Meandzija, B., Kennedy, K.A., Pham, E.T., Smaldone, L.F. Cancer Res. (1985) [Pubmed]
  20. Induction of bleomycin resistance in a human oral squamous carcinoma cell line and characterisation of bleomycin-resistant and -sensitive clones. Urade, M., Ogura, T., Uematsu, T., Takahashi, Y., Kishimoto, H., Yoshioka, W. Eur. J. Cancer, B, Oral Oncol. (1994) [Pubmed]
  21. Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization. Brömme, D., Rossi, A.B., Smeekens, S.P., Anderson, D.C., Payan, D.G. Biochemistry (1996) [Pubmed]
  22. Essential binding and functional domains of human bleomycin hydrolase. Koldamova, R.P., Lefterov, I.M., Gadjeva, V.G., Lazo, J.S. Biochemistry (1998) [Pubmed]
  23. Regional and cellular distribution of bleomycin hydrolase mRNA in human brain: comparison between Alzheimer's diseased and control brains. Malherbe, P., Faull, R.L., Richards, J.G. Neurosci. Lett. (2000) [Pubmed]
  24. Metabolic inactivation: a mechanism of human tumor resistance to bleomycin. Sebti, S.M., Jani, J.P., Mistry, J.S., Gorelik, E., Lazo, J.S. Cancer Res. (1991) [Pubmed]
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