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Thomas Jefferson University - Hideko Kaji, Ph.D.
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Hideko Kaji, Ph.D.
Biochemistry and Molecular Biology
Thomas Jefferson University
Jefferson Medical College
Department of Biochemistry & Molecular Biology
Professor
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Mailing Address
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1020 Lucust Street, Room 456A JAH
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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Translation (protein synthesis) from aminoacyl tRNA consists of four consecutive steps; initiation, elongation, termination, and recycling of the machinery of the protein synthesis for the next round of translation. We discovered the fourth step. We are working on the this step in prokaryotes and eukaryotes.
We discovered that a protein called ribosome recycling factor (RRF) is necessary for this step in prokaryotes. This protein is essential for all organisms except for Archaea. In collaboration with other laboratories, we determined the structure of RRF and the ribosomal binding site of RRF. RRF moves in the inter-subunits space of the ribosome during its function like tRNA does. We have recently discovered RRF functions to rescue stalled ribosomes with the help of termination factors RFs in the absence of the termination codon.
In the eukaryotic cytoplasmic system, there is no equivalent of RRF for recycling ribosomes. In search for the recycling factor, we discovered that eEF3 and ATP functions to disassemble the post-termination complex. eEF2 helps by translocating peptidyl tRNA to the P-site. The translocated peptidyl tRNA is hydrolyzed by eRF1 and 3 to form post-termination complexes. eIF3 has no effect on this system. Since eEF3 is limited to yeast, we are going to find out what proteins function to recycle post-termination complexes in higher eukaryotes such as human and rabbits. It is our hope that these studies will form the bases to develop anti-microbial agents in particular anti-fungal agents.
Laboratory Staff
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Publications
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- Selected Publications:
- Kaji, H., Novelli, G. D. and Kaji, A., A soluble amino acid-incorporating system from rat liver. Biochim. Biophys. Acta., 76: 474, 1963
- Kaji, A., Kaji, H. and Novelli, G. D., Soluble amino acid-incorporating system. II. Soluble nature of the system and the charcterization of the radioactive product. J. Biol. Chem., 240: 1192, 1965
- Kaji, A., Kaji, H. and Novelli, G. D., Soluble amino acid-incorporation system. I. Preparation of the system and the nature of the reaction. J. Biol. Chem., 240: 1185, 1965
- Kaji, H. and Kaji, A. Specific binding of sRNA to ribosomes: effect of streptomycin. Proc. Natl. Acad. Sci. USA, 54: 213, 1965
- Kaji, H., Suzuka, I. and Kaji, A., Binding of specific sRNA to ribosomes: binding of sRNA to the template 30S subunits complex. J. Biol. Chem., 241: 1251, 1966
- Kaji, H. and Tanaka, Y., Binding of dihydrostreptomycin to ribosomal subunits. J Mol. Biol., 32: 221,1968
- Kaji, H., Intraribosomal environment of the nascent peptide chain. Intern. Rev. Cytol., 29: 169, 1970
- Kaji, H. and Parkhouse, R. M. E., Intracellular J chain in mouse plasma cytomas secreting IgM and IgG. Nature, 24: 45, 1974
- Kaji, H. and Rao, P., Membrane modification by arginyl tRNA. FEBS Lett, 66: 194, 1976
- Kaji, H., Amino-terminal arginylation of chromosomal proteins by arginyl-tRNA. Biochemistry, 15: 5121, 1976
- Rao, P. and Kaji, H., Effect of temperature on arginine incorporation by ribosomeless extracts of cell transformed by a temperature-sensitive mutant of Rous sarcoma virus. Biochim. Biophys. Acta, 477: 394-403, 1977
- Ogata, T., Higuchi, H., Mochida, S., Matsumoto, H., Kato, A., Endo, T., Kaji, A. and Kaji, H., HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri. AIDS Res. Hum. Retroviruses, 8: 1937, 1992
- Fujihashi, T., Sakata, T., Kaji, A. and Kaji ,H., Antiviral action of oligodeoxyguanylic acids aganist human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses, 11: 461, 1995
- Fujihashi, T. Hara, H., Sakata, T., Mori, K., Higuchi, H., Tanaka, A, Kaji, A. and Kaji, H., Antihuman immunodeficiency virus (HIV) activities of halogenated gomisin J derivatives, new nonucleotide inhibitors of HIV type 1 reverse transcriptase. Antimicrob. Agents Chemother., 39: 2000, 1995
- Zhang, S., Hara, H., Kaji, A. and Kaji, H., Inhibition of HIV-1 RNA dimerization by antisense DNA corresponding to the seventeen nucleotide sequence downstream from the splice down site of HIV-1 RNA. AIDS Res. Hum. Retroviruses, 13: 865, 1997
- Luo, Z., Fan, X., Zhou, N., Hiraoka, M., Luo, J., Kaji, H. and Huang, Z., Structure-function study and anti-HIV activity of synthetic peptide analogues derived from viral chemokine vMIP-II. Biochemystry, 39: 13545, 2000
- Kaji, A., Kiel, M., Muto, A., Hirokawa, G. and Kaji, H., The fourth step of protein synthesis: Disassembly of the post-termination complex is catalyzed by elongation factor G and ribosome recycling factor, RRF, a near perfect mimic of tRNA. Cold Spring Harbor Symposium 66th, p. 515, 2001
- Hirokawa, G., Kiel, M. C., Muto, A., Selmer, M., Raj, S., Liljas, A., Igarashi, K., Kaji, H. and Kaji, A., Post-termination complex disassembly by ribosome recycling factor, a functional tRNA mimic. EMBO J., 21: 2272, 2002
- Hirokawa, G., Kiel, M.C., Muto, A., Kawai, G., Igarashi, K., Kaji, H. and Kaji, A., Binding of ribosome recycling factor (RRF) to ribosome-Comparison with tRNA. J. Biol. Chem., 277: 35847, 2002
- Zhou, N., Luo, Z., Luo, J., Fan, X., Cayabyab, M., Hiraoka, M., Liu, D., Han. X., Pesavento, J., Dong Z., Wang, Y., Kaji, H., Sodroski, J.G. and Huang Z., Exploring the stereochemistry of CXCR4-Peptide recognition and inhibiting HIV-1 entry with D-peptides derived from chemokines. J. Biol. Chem., 277: 17476, 2002
- Teyssier, E., Hirokawa, G., Tretiakova A., Jameson, B., Kaji, A. and Kaji, H., Temperature sensitive mutation in yeast mitochondrial ribosome recycling factor (RRF). Nucleic Acid Res., 31: 4218, 2003
- Kiel, M. C., Raj, S., Kaji, H. and Kaji, A., Release of ribosome-bound recycling factor (RRF) by elongation factor G. (EF-G). J. Biol. Chem., 278: 48041, 2003
- Kaji, A. and Kaji, H., The history of deciphering the genetic code; setting the record straight. Trends Biochemical Sci., 29: 293, 2004
- Hirokawa, G., Inokuchi, H., Kaji, H., Igarashi. K. and Kaji, A., In vivo effect of inactivation of ribosome recycling factor - Fate of ribosomes after unscheduled translation downstream of open reading frame. Mol. Microbiol., 54: 1011, 2004
- Yang, D., Shuda, M. and Kaji, H., Inhibition of human T-cell leukemia virus type 1 by the short oligoguanylic acids in vitro, Mater. Sci. Eng. C 24: 887-892, 2004
- Raj, V. S., Kaji, H., Kaji, A., Interaction of RRF and EF-G from E. coli and T. thermophilus with ribosomes from both origins- insight into the mechanism of the ribosome recycling step. RNA, 11:275-284, 2005
- Hirokawa, G, Nijman, R. M., Raj, V.S., Kaji, H., Igarashi, K., Kaji, A., The role of ribosome recycling factor in dissociation of 70S ribosomes into subunits. RNA, 11:1317-1128, 2005
- Kaji, A. and Kaji, H., The history of deciphering the genetic code; setting the record straight, In The Inside Story: DNA to RNA to Protein, ed. Witowski, J., 50th Anniversary of IUBMB, Cold Spring Harbor Press, p. 209, 2005
- Hirokawa, G., Demeshkina, N., Iwakura, N., Kaji, H. and Kaji, A., The Ribosome Recycling Step: Consensus or Controversy? Trends Biochemical Sci., 31, 143-149, 2006
- Demeshkina, N., Hirokawa, G., Kaji, A. and Kaji,H. Novel activity of eukaryotic translocase,eEF2:dissociation of the 80S ribosome into subunits with ATP but not with GTP. Nucleic Acids Res. 35:4597-4607, 2007
- Hirokawa, G., Kaji, H. and Kaji, A., Inhibition of Anti-Association Activity of Translation Initiation Factor 3 by Paromomycin. Antimicrob Agents Chemother., 51: 175-80, 2007.
- Kiel, M. C., Kaji, H. and Kaji, A., Ribosome Recycling: An essential process of protein synthesis. Biochem. Mol. Biol. Education, 35:40-44, 2007
- Barat, C., Datta, P. P., Raj, S., Sharma, M. R., Kaji, H., Kaji, A. and Agrawal, R. K., Progression of the Ribosome Recycling Factor through the Ribosome Dissociates theTwo Ribosomal Subunits, Mol. Cell, 27, 250-261,2007.
- Borovinskaya, M. A., Pai, R. D., Zhang, W., Schuwirth, B. S., Holton, J.M.,Hirokawa,G., Kaji,H.,Kaji, A. and Cate, J. H. D. Structural basis for aminoglycoside Inhibition of bacterial ribosome recycling, Nature Struct. & Molec. Biol., 14,727-732,2007.
- Pai, S R.D., Zhang, W., Schuwirth, B. S, Hirokawa, G. Kaji, H., Kaji, A and Cate,J., Structural Insights Into Ribosome Recycling Factor Interactions with the 70S Ribosome, J. Mol. Biol. 376, 1334-1347, 2008.
- Hirokawa, G, Iwakura, N., Kaji, A. and Kaji, H. ,The role of GTP in transient splitting of 70S ribosomes by RRF (ribosome recycling factor) and EF-G (elongation factor G), Nucleic Acids Res. 36,6676-87, 2008.
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Individual Expertise profile of
Hideko Kaji, Ph.D., Copyright © Hideko Kaji, Ph.D..
Last Updated
by Hideko Kaji, Ph.D. : Tuesday, October 13, 2009 3:59:35 PM
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