Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis

Cancer Letters

Volumn 237, Issue 2, 2006, Pages 167-179

  Liaudet Coopman, Emmanuelle ^a   Beaujouin, Mélanie ^a   Derocq, Danielle ^a   Garcia, Marcel ^a   Glondu Lassis, Murielle ^a   Laurent Matha, Valérie ^a   Prébois, Christine ^a   Rochefort, Henri ^a   Vignon, Françoise ^a  

^a INSERM   (France)

Author keywords

Angiogenesis; Apoptosis; Cancer; Cathepsin D; Metastasis; Protease

Indexed keywords

ASPARTIC PROTEINASE; BINDING PROTEIN; BIOLOGICAL MARKER; CATHEPSIN B; CATHEPSIN D; CATHEPSIN L; CELL SURFACE RECEPTOR; CYSTEINE; LYSOSOME ENZYME; MITOGENIC AGENT;

ANGIOGENESIS; APOPTOSIS; BREAST CANCER; CANCER CELL; CANCER GROWTH; CANCER INCIDENCE; CANCER INHIBITION; CARCINOGENICITY; CELL ACTIVITY; CELL GROWTH; CELL PROLIFERATION; CELL SECRETION; CELL STIMULATION; CLINICAL TRIAL; ENZYME RELEASE; ENZYME SUBSTRATE; EPITHELIUM CELL; FIBROBLAST; GENE MUTATION; HUMAN; META ANALYSIS; METASTASIS; NONHUMAN; PARACRINE SIGNALING; PATHOGENESIS; PATHOPHYSIOLOGY; PH; PRIORITY JOURNAL; PROGNOSIS; PROTEIN DEGRADATION; PROTEIN EXPRESSION; SHORT SURVEY; STROMA CELL; SYSTEMATIC REVIEW; TUMOR GROWTH;

EID: 33646854205     PISSN: 03043835     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.canlet.2005.06.007     Document Type: Review

References (125)

1. de Duve C. Lysosomes revisited. Eur. J. Biochem. 137 (1983) 391-397 (Review)
2. Urbich C., Heeschen C., Aicher A., Sasaki K., Bruhl T., Farhadi M.R., et al. Cathepsin L is required for endothelial progenitor cell-induced neovascularization. Nat. Med. 11 (2005) 206-213
3. Nakagawa T., Roth W., Wong P., Nelson A., Farr A., Deussing J., et al. Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science 280 (1998) 450-453
4. Saftig P., Hetman M., Schmahl W., Weber K., Heine L., Mossmann H., et al. Mice deficient for the lysosomal proteinase cathepsin D exhibit progressive atrophy of the intestinal mucosa and profound destruction of lymphoid cells. Eur. Mol. Bio. J. 14 (1995) 3599-3608
5. Koike M., Nakanishi H., Saftig P., Ezaki J., Isahara K., Ohsawa Y., et al. Cathepsin D deficiency induces lysosomal storage with ceroid lipofuscin in mouse CNS neurons. J. Neurosci. 20 (2000) 6898-6906
6. Nakanishi H., Zhang J., Koike M., Nishioku T., Okamoto Y., Kominami E., et al. Involvement of nitric oxide released from microglia-macrophages in pathological changes of cathepsin D-deficient mice. J. Neurosci. 21 (2001) 7526-7533
7. Koike M., Shibata M., Ohsawa Y., Nakanishi H., Koga T., Kametaka S., et al. Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice. Mol. Cell. Neurosci. 22 (2003) 146-161
8. Koblinski J.E., Ahram M., and Sloane B.F. Unraveling the role of proteases in cancer. Clin. Chim. Acta. 291 (2000) 113-135 (Review)
9. Laurent-Matha V., Maruani-Herrmann S., Prébois C., Beaujouin M., Glondu M., Noël A., et al. Catalytically-inactive human cathepsin D triggers fibroblast invasive growth. J. Cell Biol. 168 (2005) 489-499
10. Fehrenbacher N., and Jaattela M. Lysosomes as targets for cancer therapy. Cancer Res. 65 (2005) 2993-2995
11. Rochefort H., and Liaudet-Coopman E. Cathepsin D in cancer metastasis: a protease and a ligand. APMIS 107 (1999) 86-95
12. Turk V., Kos J., and Turk B. Cysteine cathepsins (proteases)-on the main stage of cancer?. Cancer Cell 5 (2004) 409-410
13. Joyce J.A., Baruch A., Chehade K., Meyer-Morse N., Giraudo E., Tsai F.Y., et al. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5 (2004) 443-453
14. Barrett A.J. Cathepsin D: purification of isoenzymes from human and chicken liver. Biochem. J. 117 (1970) 601-607
15. Diment S., Martin K.J., and Stahl P.D. Cleavage of parathyroid hormone in macrophage endosomes illustrates a novel pathway for intracellular processing of proteins. J. Biol. Chem. 264 (1989) 13403-13406
16. Briozzo P., Morisset M., Capony F., Rougeot C., and Rochefort H. In vitro degradation of extracellular matrix with Mr 52,000 cathepsin D secreted by breast cancer cells. Cancer Res. 48 (1988) 3688-3692
17. Umezawa H., Aoyagi T., Morishima H., Matsuzaki M., Hamada M., and Takeuchi T. Pepstatin, a new pepsin inhibitor produced by Actinomycetes. J. Antibiot. 23 (1970) 259-262
18. Metcalf P., and Fusek M. Two crystal structures for cathepsin D: the lysosomal targeting signal and active site. Eur. Mol. Biol. Org. J. 12 (1993) 1293-1302
19. Baldwin E.T., Bhat T.N., Gulnik S., Hosur M.V., Sowder II R.C., Cachau R.E., et al. Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design. Proc. Natl Acad. Sci. USA 90 (1993) 6796-6800
20. Lee A.Y., Gulnik S.V., and Erickson J.W. Conformational switching in an aspartic proteinase. Nat. Struct. Biol. 5 (1998) 866-871
21. Ishidoh K., and Kominami E. Processing and activation of lysosomal proteinases. Biol. Chem. 383 (2002) 1827-1831
22. Tang J., and Wong R.N. Evolution in the structure and function of aspartic proteases. J. Cell. Biochem. 33 (1987) 53-63
23. Hsueh W.A., and Baxter J.D. Human prorenin. Hypertension 17 (1991) 469-477
24. Richo G., and Conner G.E. Proteolytic activation of human procathepsin D. Adv. Exp. Med. Biol. 306 (1991) 289-296
25. Conner G.E., and Richo G. Isolation and characterization of a stable activation intermediate of the lysosomal aspartyl protease cathepsin D. Biochem. 31 (1992) 1142-1147
26. Larsen L.B., and Boisen A. Procathepsin D cannot autoactivate to cathepsin D at acid pH. Fed. Eur. Biochem. Soc. Lett. 319 (1993) 54-58
27. Hasilik A., and Neufeld E.F. Biosynthesis of lysosomal enzymes in fibroblasts. Synthesis as precursors of higher molecular weight. J. Biol. Chem. 255 (1980) 4937-4945
28. Richo G., and Conner G.E. Structural requirements of procathepsin D activation and maturation. J. Biol. Chem. 269 (1994) 14806-14812
29. Von Figura K., and Hasilik A. Lysosomal enzymes and their receptors. Annu. Rev. Biochem. 55 (1986) 167-193
30. Kornfeld S. Lysosomal enzyme targeting. Biochem. Soc. Trans. 18 (1990) 367-374
31. Hentze M., Hasilik A., and von Figura K. Enhanced degradation of cathepsin D synthesized in the presence of the threonine analog beta-hydroxynorvaline. Arch. Biochem. Biophys. 230 (1984) 375-382
32. Samarel A.M., Ferguson A.G., Decker R.S., and Lesch M. Effects of cysteine protease inhibitors on rabbit cathepsin D maturation. Am. J. Physiol. 257 (1989) 1069-1079
33. Rijnboutt S., Kal A.J., Geuze H.J., Aerts H., and Strous G.J. Mannose 6-phosphate-independent targeting of cathepsin D to lysosomes in HepG2 cells. J. Biol. Chem. 266 (1991) 23586-23592
34. Capony F., Braulke T., Rougeot C., Roux S., Montcourrier P., and Rochefort H. Specific mannose-6-phosphate receptor-independent sorting of pro-cathepsin D in breast cancer cells. Exp. Cell Res. 215 (1994) 154-163
35. Gieselmann V., Hasilik A., and von Figura K. Processing of human cathepsin D in lysosomes in vitro. J. Biol. Chem. 260 (1985) 3215-3220
36. Duffy M.J. Proteases as prognostic markers in cancer. Clin. Cancer Res. 2 (1996) 613-618
37. Felbor U., Kessler B., Mothes W., Goebel H.H., Ploegh H.L., Bronson R.T., et al. Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc. Natl Acad. Sci. USA 99 (2002) 7883-7888
38. Wille A., Gerber A., Heimburg A., Reisenauer A., Peters C., and Saftig P. Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells. Biol. Chem. 385 (2004) 665-670
39. Kobayashi T., Honke K., Gasa S., Fujii T., Maguchi S., Miyazaki T., et al. Proteolytic processing sites producing the mature form of human cathepsin D. Int. J. Biochem. 24 (1992) 1487-1491
40. Erickson A.H., and Blobel G. Carboxyl-terminal proteolytic processing during biosynthesis of the lysosomal enzymes beta-glucuronidase and cathepsin D. Biochemistry 22 (1983) 5201-5205
41. Laurent-Matha V., Farnoud M.R., Lucas A., Rougeot C., Garcia M., and Rochefort H. Endocytosis of pro-cathepsin D into breast cancer cells is mostly independent of mannose-6-phosphate receptors. J. Cell. Sci. 111 (1998) 2539-2549
42. Laurent-Matha V., Lucas A., Huttler S., Sandhoff K., Garcia M., and Rochefort H. Procathepsin D interacts with prosaposin in cancer cells but its internalization is not mediated by LDL receptor-related protein. Exp. Cell. Res. 277 (2002) 210-219
43. Vignon F., Capony F., Chambon M., Freiss G., and Rochefort H. Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52 K protein. Endocrinology 118 (1986) 1537-1545
44. Clague M.J. Molecular aspects of the endocytic pathway. Biochem. J. 336 (1998) 271-282
45. Hasilik A., von Figura K., Conzelmann E., Nehrkorn H., and Sandhoff K. Lysosomal enzyme precursors in human fibroblasts. Activation of cathepsin D precursor in vitro and activity of beta-hexosaminidase A precursor towards ganglioside GM2. Eur. J. Biochem. 125 (1982) 317-321
46. Rochefort H., Cavaillès V., Augereau P., Capony F., Maudelonde T., Touitou I., et al. Overexpression and hormonal regulation of pro-cathepsin D in mammary and endometrial cancer. J. Steroid Biochem. 34 (1989) 177-182
47. Cavaillès V., Augereau P., and Rochefort H. Cathepsin D gene is controlled by a mixed promoter and estrogens stimulate only TATA dependent transcription in breast cancer cells. Proc. Natl Acad. Sci. USA 90 (1993) 203-207
48. Augereau P., Garcia M., Mattei M.G., Cavaillès V., Depadova F., Derocq D., et al. Cloning and sequencing of the 52K cathepsin D cDNA of MCF7 breast cancer cells and mapping on chromosome 11. Mol. Endo. 2 (1988) 186-192
49. Westley B.R., and May F.E. Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human breast cancer cells. Nucl. Acids. Res. 15 (1987) 3773-3786
50. Cavaillès V., Garcia M., and Rochefort H. Regulation of cathepsin D and pS2 gene expression by growth factors in MCF7 human breast cancer cells. Mol. Endocrinol. 3 (1989) 552-558
51. Augereau P., Mirallès F., Cavaillès V., Gaudelet C., Parker M., and Rochefort H. Characterization of the proximal estrogen responsive element of human cathepsin D gene. Mol. Endocrinol. 8 (1994) 693-703
52. Capony F., Rougeot C., Montcourrier P., Cavaillès V., Salazar G., and Rochefort H. Increased secretion, altered processing, and glycosylation of pro-cathepsin D in human mammary cancer cells. Cancer Res. 49 (1989) 3904-3909
53. Rochefort H. Cathepsin D in breast cancer: a tissue marker associated with metastasis. Eur. J. Cancer 28A (1992) 1780-1783
54. Westley B.R., and May F.E. Prognostic value of cathepsin D in breast cancer. Br. J. Cancer 79 (1999) 189-190
55. Ferrandina G., Scambia G., Bardelli F., Panici B., Mancuso S., and Messori A. Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis. Br. J. Cancer 76 (1997) 661-666
56. Foekens J.A., Look M.P., Bolt-de Vries J., Meijer-van Gelder M., van Putten W.L.J., and Klijn J.G.M. Cathepsin D in primary breast cancer: prognostic evaluation involving 2810 patients. Br. J. Cancer 79 (1999) 300-307
57. Roger P., Montcourrier P., Maudelonde T., Brouillet J.P., Pagès A., Laffargue F., et al. Cathepsin D immunostaining in paraffin-embedded breast cancer cells and macrophages. Correlation with cytosolic assay. Human Path. 25 (1994) 863-871
58. Escot C., Zhao Y., Puech C., and Rochefort H. Cellular localisation by in situ hybridisation of cathepsin D, stromelysin 3, and urokinase plasminogen activator RNAs in breast cancer. Breast Cancer Res. Treat. 38 (1996) 217-226
59. Joensuu H., Toikkanen S., and Isola J. Stromal cell cathepsin D expression and long-term survival in breast cancer. Br. J. Cancer 71 (1995) 155-159
60. Nadji M., Fresno M., Nassiri M., Conner G., Herrero A., and Morales A.R. Cathepsin D in host stromal cells, but not in tumor cells, is associated with aggressive behavior in node-negative breast cancer. Hum. Pathol. 27 (1996) 890-895
61. O'Donoghue A.E., Poller D.N., Bell J.A., Galea M.H., Elston C.W., Blamey R.W., et al. Cathepsin D in primary breast carcinoma: adverse prognosis is associated with expression of cathepsin D in stromal cells. Breast Cancer Res. Treat. 33 (1995) 137-145
62. Têtu B., Brisson J., Lapointe H., Wang C.S., Bernard P., and Blanchette C. Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases. Breast Cancer Res. Treat. 55 (1999) 137-147
63. Brouillet J.P., Dufour F., Lemamy G., Garcia M., Schlup N., Grenier J., et al. Increased cathepsin D level in serum of patients with metastatic breast carcinoma detected with a specific pro-cathepsin D immunoassay. Cancer 79 (1997) 2132-2136
64. Jarosz D.E., Hamer P.J., Tenney D.Y., and Zabrecky J.R. Elevated levels of pro-cathepsin D in the plasma of breast cancer patients. Int. J. Oncol. 6 (1995) 859-865
65. Garcia M., Derocq D., Pujol P., and Rochefort H. Overexpression of transfected cathepsin D in transformed cells increases their malignant phenotype and metastatic potency. Oncogene 5 (1990) 1809-1814
66. Liaudet E., Garcia M., and Rochefort H. Cathepsin D maturation and its stimulatory effect on metastasis are prevented by addition of KDEL retention signal. Oncogene 9 (1994) 1145-1154
67. Liaudet E., Derocq D., Rochefort H., and Garcia M. Transfected cathepsin D stimulates high density cancer cell growth by inactivating secreted growth inhibitors. Cell Growth Differ. 6 (1995) 1045-1052
68. Glondu M., Coopman P., Laurent-Matha V., Garcia M., and Rochefort H. A mutated cathepsin-D devoid of its catalytic activity stimulates the growth of cancer cells. Oncogene 20 (2001) 6920-6929
69. Berchem G.J., Glondu M., Gleizes M., Brouillet J.P., Garcia M., and Liaudet-Coopman E. Cathepsin-D affects multiple steps of tumor progression: Proliferation, angiogenesis and apoptosis. Oncogene 51 (2002) 5951-5955
70. Glondu M., Liaudet-Coopman E., Derocq D., Platet N., Rochefort H., and Garcia M. Down-regulation of cathepsin-D by antisense gene transfer inhibits tumor growth and metastatic potential of human breast cancer cells. Oncogene 21 (2002) 5127-5134
71. Fusek M., and Vetvicka V. Mitogenic function of human procathepsin D: the role of the propeptide. Biochem. J. 303 (1994) 775-780
72. Vetvicka V., Vektvickova J., and Fusek M. Effect of human cathepsin D on proliferation of human cell lines. Cancer Lett. 79 (1994) 131-135
73. Vetvicka V., Vetvickova J., and Fusek M. Effect of procathepsin D and its activation peptide on prostate cancer cells. Cancer Lett. 129 (1998) 55-59
74. Vetvicka V., Vetvickova J., Hilgert I., Voburka Z., and Fusek M. Analysis of the interaction of procathepsin D activation peptide with breast cancer cells. Int. J. Cancer 73 (1997) 403-409
75. Vetvicka V., Vetvickova J., and Fusek M. Anti-human procathepsin D activation peptide antibodies inhibit breast cancer development. Breast Cancer Res. Treat. 57 (1999) 261-269
76. Vetvicka V., Vetvickova J., and Fusek M. Role of procathepsin D activation peptide in prostate cancer growth. Prostate 44 (2000) 1-7
77. Briozzo P., Badet J., Capony F., Pieri I., Montcourrier P., Barritault D., et al. Rochefort, MCF7 mammary cancer cells respond to bFGF and internalize it following its release from extracellular matrix: a permissive role of cathepsin D. Exp. Cell Res. 194 (1991) 252-259
78. Rifkin D.B. Cross-talk among proteases and matrix in the control of growth factor action. Fibrinolysis Proteolysis 11 (1997) 3-9
79. Griffiths J.R. Are cancer cells acidic?. Br. J. Cancer 64 (1991) 425-427
80. Folkman J. Anti-angiogenesis: new concept for therapy of solid tumors. Ann. Sug. 175 (1972) 409-416
81. Pepper M.S. Role of the matrix metalloproteinase and plasminogen activator-plasminsystems in angiogenesis. Arterioscler. Thromb. Vasc. Biol. 21 (2001) 1104-1117
82. Gonzalez-Vela M.C., Garijo M.F., Fernandez F., Buelta L., and Val-Bernal J.F. Cathepsin-D in host stromal cells is associated with more highly vascular and aggressive invasive breast carcinoma. Histopathology 34 (1999) 35-42
83. Morikawa W., Yamamoto K., Ishikawa S., Takemoto S., Ono M., Fukushi J., et al. Angiostatin generation by cathepsin-D secreted by human prostate carcinoma cells. J. Biol. Chem. 275 (2000) 38912-38920
84. Piwnica D., Touraine P., Struman I., Tabruyn S., Bolbach G., Clapp C., et al. Mol. Endocrinol. 18 (2004) 2522-2542
85. Elenbaas B., and Weinberg R.A. Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. Exp. Cell Res. 264 (2001) 169-184
86. Liotta L.A., and Kohn E.C. The microenvironment of the tumor-host interface. Nature 411 (2001) 375-379
87. Grinnell F. Fibroblasts, myofibroblasts, and wound contraction. J. Cell Biol. 124 (1994) 401-404
88. Basset P., Bellocq J.P., Wolf C., Stoll I., Hutin P., Limacher J.M., et al. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 348 (1990) 699-704
89. Olumi A.F., Grossfeld G.D., Hayward S.W., Caroll P.R., Tslty T.D., and Cunha G.R. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 59 (1999) 5002-5011
90. Shekhar M.P., Werdell J., Santner S.J., Pauley R.J., and Tait L. Breast stroma plays a dominant regulatory role in breast epithelial growth and differentiation: implications for tumor development and progression. Cancer Res. 61 (2001) 1320-1326
91. Ingber D.E., and Folkman J. How does extracellular matrix control capillary morphogenesis?. Cell 58 (1989) 803-805
92. Juliano R.L., and Haskill S. Signal transduction from the extracellular matrix. J. Cell. Biol 120 (1993) 577-585
93. Assoian R.K., and Marcantonio E.E. The extracellular matrix as a cell cycle control element in atherosclerosis and restenosis. J. Clin. Invest. 98 (1996) 2436-2439
94. Lin C.Q., and Bissell M.J. Multi-faceted regulation of cell differentiation by extracellular matrix. Fed. Am. Soc. Exp. Biol. J. 7 (1993) 737-743
95. Koblinski J.E., Dosescu J., Sameni M., Moin K., Clark K., and Sloane B.F. Interaction of human breast fibroblasts with collagen I increased secretion of procathepsin B. J. Biol. Chem. 277 (2002) 32220-32227
96. McKinnon T., Chakraborty C., Gleeson L.M., Chidiac P., and Lala P.K. Stimulation of human extravillous trophoblast migration by IGF-II is mediated by IGF type 2 receptor involving inhibitory G protein(s) and phosphorylation of MAPK. J. Clin. Endocrinol. Metab. 86 (2001) 3665-3674
97. Heylen N., Vincent L.M., Devos V., Dubois V., Remacle C., and Trouet A. Fibroblasts capture cathepsin D secreted by breast cancer cells: possible role in the regulation of the invasive process. Int. J. Cancer 20 (2002) 761-767
98. Uria J.A., Stahle-Backdahl M., Seiki M., Fueyo A., and Lopez-Otin C. Regulation of collagenase-3 expression in human breast carcinomas is mediated by stromal-epithelial cell interactions. Cancer Res. 57 (1997) 4882-4888
99. Christensen L., Wiborg Simonsen A.C., Heegaard C.W., Moestrup S.K., Andersen J.A., and Andreasen P.A. Immunohistochemical localization of urokinase-type plasminogen activator, type-1 plasminogen-activator inhibitor, urokinase receptor and alpha(2)-macroglobulin receptor in human breast carcinomas. Int. J. Cancer 66 (1996) 441-452
100. Liotta L.A., Steeg P.S., and Stetler-Stevenson W.G. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64 (1991) 327-336
101. Chambers A.F., and Matrisian L.M. Changing views of the role of matrix metalloproteinases in metastasis. J. Natl Cancer Inst. 89 (1997) 1260-1270
102. Carney D.H., and Cunningham D.D. Role of specific cell surface receptors in thrombin-stimulated cell division. Cell 15 (1978) 1341-1349
103. Rochefort H., Capony F., Garcia M., Cavaillès V., Freiss G., Chambon M., et al. Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis?. J. Cell. Biochem. 35 (1987) 17-29
104. Kane S.E., and Gottesman M.M. The role of cathepsin L in malignant transformation. Semin. Cancer Biol. 1 (1990) 127-136
105. Mathieu M., Rochefort H., Barenton B., Prebois C., and Vignon F. Interactions of cathepsin-D and insulin-like growth factor-II (IGF-II) on the IGF-II/mannose-6-phosphate receptor in human breast cancer cells and possible consequences on mitogenic activity of IGF-II. Mol Endocrinol. 4 (1990) 1327-1335
106. Deiss L.P., Galinka H., Berissi H., and Cohen O. Cathepsin D protease mediates programmed cell death induced by interferon gamma. Eur. Mol. Biol. Org. J. 15 (1996) 3861-3870
107. Wu G.S., Saftig P., Peters C., and El-Deiry W.S. Potential role of cathepsin D in p53-dependent tumor suppression and chemosensitivity. Oncogene 16 (1998) 2177-2183
108. Roberg K., and Ollinger K. Oxidative stress causes relocation of the lysosomal enzyme cathepsin D with ensuing apoptosis in neonatal rat cardiomyocytes. Am. J. Pathol. 152 (1998) 1151-1156
109. Ollinger K. Inhibition of cathepsin D prevents free-radical-induced apoptosis in rat cardiomyocytes. Arch. Biochem. Biophys. 373 (2000) 346-351
110. Roberg K. Relocalization of cathepsin D and cytochrome c early in apoptosis revealed by immunoelectron microscopy. Lab. Invest. 81 (2001) 149-158
111. Kagedal K., Johansson U., and Öllinger K. The lysosomal protease cathepsin D mediates apoptosis induced by oxidative stress. Fed. Am. Soc. Exp. Biol. J. 15 (2001) 1592-1594
112. Takuma K., Kiriu M., Mori K., Lee E., Enomoto R., Baba A., et al. Matsuda, Roles of cathepsins in reperfusion-induced apoptosis in cultured astrocytes. Neurochem. Int. 42 (2003) 153-159
113. Johansson A.C., Steen H., Öllinger K., and Roberg K. Cathepsin D mediates cytochrome c release and caspase activation in human fibroblast apoptosis induced by staurosporine. Cell Death Differ. 10 (2003) 1253-1259
114. Emert-Sedlak L., Shangary S., Rabinovitz A., Miranda M.B., Delach S.M., and Johnson D.E. Involment of cathepsin D in chemotherapy-induced cytochrome c release, caspase activation, and cell death. Mol. Cancer Ther. 4 (2005) 733-742
115. Roberg K., Kagedal K., and Ollinger K. Microinjection of cathepsin d induces caspase-dependent apoptosis in fibroblasts. Am. J. Pathol. 161 (2002) 89-96
116. Heinrich M., Neumeyer J., Jakob M., Hallas C., Tchikov V., Winoto-Morbach S., et al. Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation. Cell Death Differ. 11 (2004) 550-563
117. Bidère N., Lorenzo H.K., Carmona S., Laforge M., Harper F., Dumont C., et al. Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J. Biol. Chem. 278 (2003) 31401-31411
118. Terman A., Neuzil J., Kagedal K., Ollinger K., and Brunk U.T. Decreased apoptotic response of inclusion-cell disease fibroblasts: a consequence of lysosomal enzyme missorting?. Exp. Cell Res. 274 (2002) 9-15
119. Demoz M., Castino R., Cesaro P., Baccino F.M., Bonelli G., and Isidoro C. Endosomal-lysosomal proteolysis mediates death signalling by TNFalpha, not by etoposide, in L929 fibrosarcoma cells: evidence for an active role of cathepsin D. Biol. Chem. 383 (2002) 1237-1248
120. Shibata M., Kanamori S., Isahara K., Ohsawa Y., Konishi A., Kametaka S., et al. Participation of cathepsins B and D in apoptosis of PC12 cells following serum deprivation. Res. Commun. 251 (1998) 199-203
121. Gottlieb R.A., Nordberg J., Skowronski E., and Babior B.M. Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification. Proc. Natl Acad. Sci. USA 93 (1996) 654-658
122. Matsuyama S., Llopis J., Deveraux Q.L., Tsien R.Y., and Reed J.C. Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis. Nat. Cell Biol. 2 (2000) 318-325
123. Capony F., Morisset M., Barrett A.J., Capony J.P., Broquet P., Vignon F., et al. Phosphorylation, glycosylation, and proteolytic activity of the 52-kD estrogen-induced protein secreted by MCF7 cells. J. Cell Biol. 104 (1987) 253-262
124. Tardy C., Tyynela J., Hasilik A., Levade T., and Andrieu-Abadie N. Stress-induced apoptosis is impaired in cells with a lysosomal targeting defect but is not affected in cells synthesizing a catalytically inactive cathepsin D. Cell Death Differ. 10 (2003) 1090-1100
125. Reiners Jr. J.J., Caruso J.A., Mathieu P., Chelladurai B., Yin X.M., and Kessel D. Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves Bid cleavage. Cell Death Differ. 9 (2002) 934-944