New functional aspects of cathepsin D and cathepsin E

Takayuki Tsukuba, Kuniaki Okamoto, Yoshiyuki Yasuda, Wataru Morikawa, Hiroshi Nakanishi, Kenji Yamamoto

研究成果: ジャーナルへの寄稿評論記事

67 引用 (Scopus)

抄録

Cathepsin D (CD) and cathepsin E are representative lysosomal and nonlysosomal aspartic proteinases, respectively, and play an important role in the degradation of proteins, the generation of bioactive proteins, antigen processing, etc. Recenty, several lines of evidence have suggested the involvement of these two enzymes in the execution of neuronal death pathways induced by aging, transient forebrain ischemia, and excessive stimulation of glutamate receptors with excitotoxins. CD has also been shown to mediate apoptosis induced by various stimuli and p53-dependent tumor suppression. To gain more insight into in vivo functions of CD, mice deficient in this enzyme were generated. The mutant animals showed a progressive atrophy of the intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin, and developed a phenotype resembling neuronal ceroid lipofucinosis, suggesting that CD is essential for proteolysis of proteins regulating cell growth and tissue homeostasis. It has also been shown that CD molecules secreted from human prostate carcinoma cells are responsible for the generation of angiostatin, a potent endogenous inhibitor of angiogenesis, suggesting its contribution to the prevention of tumor growth and angiogenesis-dependent growth of metastases. Interestingly, pro-CD from human breast carcinoma cells showed a significantly lower angiostatin-generating activity than that from prostate carcinoma cells. Since deglycosylated CD molecules from both carcinoma cells showed a low angiostatin-generating activity, this discrepancy appeared to be attributed to the difference in the carbohydrate structures of CD molecules between the two cell types and to contribute to their potency to prevent tumor growth and metastases.

元の言語英語
ページ(範囲)601-611
ページ数11
ジャーナルMolecules and Cells
10
発行部数6
DOI
出版物ステータス出版済み - 12 31 2000

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Cathepsin E
Cathepsin D
Angiostatins
Ceroid
Growth
Carcinoma
Proteolysis
Prostate
Neoplasm Metastasis
Aspartic Acid Proteases
Lipofuscin
Neoplasms
Angiogenesis Inhibitors
Neurotoxins
Antigen Presentation
Glutamate Receptors
Enzymes
Intestinal Mucosa
Prosencephalon
Atrophy

All Science Journal Classification (ASJC) codes

  • Medicine(all)

これを引用

Tsukuba, T., Okamoto, K., Yasuda, Y., Morikawa, W., Nakanishi, H., & Yamamoto, K. (2000). New functional aspects of cathepsin D and cathepsin E. Molecules and Cells, 10(6), 601-611. https://doi.org/10.1007/s10059-000-0601-8

New functional aspects of cathepsin D and cathepsin E. / Tsukuba, Takayuki; Okamoto, Kuniaki; Yasuda, Yoshiyuki; Morikawa, Wataru; Nakanishi, Hiroshi; Yamamoto, Kenji.

:: Molecules and Cells, 巻 10, 番号 6, 31.12.2000, p. 601-611.

研究成果: ジャーナルへの寄稿評論記事

Tsukuba, T, Okamoto, K, Yasuda, Y, Morikawa, W, Nakanishi, H & Yamamoto, K 2000, 'New functional aspects of cathepsin D and cathepsin E', Molecules and Cells, 巻. 10, 番号 6, pp. 601-611. https://doi.org/10.1007/s10059-000-0601-8
Tsukuba T, Okamoto K, Yasuda Y, Morikawa W, Nakanishi H, Yamamoto K. New functional aspects of cathepsin D and cathepsin E. Molecules and Cells. 2000 12 31;10(6):601-611. https://doi.org/10.1007/s10059-000-0601-8
Tsukuba, Takayuki ; Okamoto, Kuniaki ; Yasuda, Yoshiyuki ; Morikawa, Wataru ; Nakanishi, Hiroshi ; Yamamoto, Kenji. / New functional aspects of cathepsin D and cathepsin E. :: Molecules and Cells. 2000 ; 巻 10, 番号 6. pp. 601-611.
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