This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Santamaría, I. Articles by López-Otín, C. Search for Related Content PubMed PubMed Citation Articles by Santamaría, I. Articles by López-Otín, C.

Cathepsin L2, a Novel Human Cysteine Proteinase Produced by Breast and Colorectal Carcinomas¹

Departamento de Bioquímica y Biología Molecular [I. S., G. V., C. L-O.] and Biología Funcional [A. F.], Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, and Departamento de Anatomía Patológica, Hospital Clínico-Barcelona, 08036 Barcelona, [M. C., E. C.], Spain

We have identified and cloned a new member of the papain family of cysteine proteinases from a human brain cDNA library. The isolated cDNA codes for a polypeptide of 334 amino acids that exhibits all of the structural features characteristic of cysteine proteinases, including the active site cysteine residue essential for peptide hydrolysis. Pairwise comparisons of this amino acid sequence with the remaining human cysteine proteinases identified to date showed a high percentage of identity (78%) with cathepsin L; the percentage of identity with all other members of the family was much lower (<40%). On the basis of these structural characteristics, we have tentatively called this novel protein cathepsin L2. The cDNA encoding the mature cathepsin L2 was expressed in Escherichia coli, and after purification, the recombinant protein was able to degrade the synthetic peptide benzyloxycarbonyl-L-phenylalanyl-L-arginine-7-amido-4-methylcoum

arin, which is commonly used as a substrate for cysteine proteinases. Cathepsin L2 proteolytic activity on this substrate was abolished by trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, an inhibitor of cysteine proteinases, thus providing additional evidence that the isolated cDNA encodes a functional cysteine proteinase. Northern blot analysis of polyadenylated RNAs isolated from a variety of human tissues demonstrated that cathepsin L2 is predominantly expressed in the thymus and testis. This finding is in marked contrast with the wide tissue distribution of most cysteine proteinases characterized to date, including cathepsin L, and suggests that cathepsin L2 may play a specialized role in the thymus and testis. Expression analysis of cathepsin L2 in human tumors revealed a widespread expression in colorectal and breast carcinomas but not in normal colon or mammary gland or in peritumoral tissues. Cathepsin L2 was also expressed by colorectal and breast cancer cell lines as well as by some tumors of diverse origin, including ovarian and renal carcinomas. These results open the possibility that this novel enzyme may be involved in tumor processes, as already reported for other cysteine proteinases, including cathepsin L.

¹ Supported by Grant SAF97-0258 from the Comisión Interministerial de Ciencia y Tecnología, Grant BMH4-CT96-0017 from European Union-BIOMED II, Maraton TV3 Cancer (to E. C.), and Glaxo-Wellcome, Spain. I. S. is a recipient of a fellowship from Ministerio de Educación y Ciencia (Spain).

² To whom requests for reprints should be addressed, at Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain. Phone: 34-85-104201; Fax: 34-85-103564/34-85-232255; E-mail: CLO@DWARF1.QUIMICA.UNIOVI.ES.

Received 11/21/97. Accepted 2/25/98.

This article has been cited by other articles:

				D. Bakthavatsalam, D. A. Brock, N. N. Nikravan, K. D. Houston, R. D. Hatton, and R. H. Gomer The secreted Dictyostelium protein CfaD is a chalone J. Cell Sci., August 1, 2008; 121(15): 2473 - 2480. [Abstract] [Full Text] [PDF]

				R. E. Burden, P. Snoddy, R. J. Buick, J. A. Johnston, B. Walker, and C. J. Scott Recombinant cathepsin S propeptide attenuates cell invasion by inhibition of cathepsin L-like proteases in tumor microenvironment Mol. Cancer Ther., March 1, 2008; 7(3): 538 - 547. [Abstract] [Full Text] [PDF]

				D. H.-K. Ma, J.-Y. Yao, M.-T. Kuo, L.-C. See, K.-Y. Lin, S.-C. Chen, J.-K. Chen, A.-S. Chao, S.-F. Wang, and K.-K. Lin Generation of Endostatin by Matrix Metalloproteinase and Cathepsin from Human Limbocorneal Epithelial Cells Cultivated on Amniotic Membrane Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 644 - 651. [Abstract] [Full Text] [PDF]

				T. Cheng, K. Hitomi, I. M. J. J. van Vlijmen-Willems, G. J. de Jongh, K. Yamamoto, K. Nishi, C. Watts, T. Reinheckel, J. Schalkwijk, and P. L. J. M. Zeeuwen Cystatin M/E Is a High Affinity Inhibitor of Cathepsin V and Cathepsin L by a Reactive Site That Is Distinct from the Legumain-binding Site: A NOVEL CLUE FOR THE ROLE OF CYSTATIN M/E IN EPIDERMAL CORNIFICATION J. Biol. Chem., June 9, 2006; 281(23): 15893 - 15899. [Abstract] [Full Text] [PDF]

				P. V. Gordon, J. B. Paxton, J. F. Kuemmerle, and N. S. Fox A 14-kDa cathepsin L-derived carboxyl IGFBP-2 fragment is sequestered by cultured rat ileal crypt cells Am J Physiol Gastrointest Liver Physiol, July 1, 2005; 289(1): G79 - G87. [Abstract] [Full Text] [PDF]

				K. Ravanko, K. Jarvinen, J. Helin, N. Kalkkinen, and E. Holtta Cysteine Cathepsins Are Central Contributors of Invasion by Cultured Adenosylmethionine Decarboxylase-Transformed Rodent Fibroblasts Cancer Res., December 15, 2004; 64(24): 8831 - 8838. [Abstract] [Full Text] [PDF]

				Y. Yasuda, Z. Li, D. Greenbaum, M. Bogyo, E. Weber, and D. Bromme Cathepsin V, a Novel and Potent Elastolytic Activity Expressed in Activated Macrophages J. Biol. Chem., August 27, 2004; 279(35): 36761 - 36770. [Abstract] [Full Text] [PDF]

				X. S. Puente and C. Lopez-Otin A Genomic Analysis of Rat Proteases and Protease Inhibitors Genome Res., April 1, 2004; 14(4): 609 - 622. [Abstract] [Full Text] [PDF]

				C. A. Iacobuzio-Donahue, R. Ashfaq, A. Maitra, N. V. Adsay, G. L. Shen-Ong, K. Berg, M. A. Hollingsworth, J. L. Cameron, C. J. Yeo, S. E. Kern, et al. Highly Expressed Genes in Pancreatic Ductal Adenocarcinomas: A Comprehensive Characterization and Comparison of the Transcription Profiles Obtained from Three Major Technologies Cancer Res., December 15, 2003; 63(24): 8614 - 8622. [Abstract] [Full Text] [PDF]

				J. Bania, E. Gatti, H. Lelouard, A. David, F. Cappello, E. Weber, V. Camosseto, and P. Pierre Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs PNAS, May 27, 2003; 100(11): 6664 - 6669. [Abstract] [Full Text] [PDF]

				D.P. Dickinson CYSTEINE PEPTIDASES OF MAMMALS: THEIR BIOLOGICAL ROLES AND POTENTIAL EFFECTS IN THE ORAL CAVITY AND OTHER TISSUES IN HEALTH AND DISEASE Critical Reviews in Oral Biology & Medicine, May 1, 2002; 13(3): 238 - 275. [Abstract] [Full Text] [PDF]

				W. ROTH, J. DEUSSING, V. A. BOTCHKAREV, M. PAULY-EVERS, P. SAFTIG, A. HAFNER, P. SCHMIDT, W. SCHMAHL, J. SCHERER, I. ANTON-LAMPRECHT, et al. Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling FASEB J, October 1, 2000; 14(13): 2075 - 2086. [Abstract] [Full Text]

				I. Santamaria, G. Velasco, A. M. Pendas, A. Paz, and C. Lopez-Otin Molecular Cloning and Structural and Functional Characterization of Human Cathepsin F, a New Cysteine Proteinase of the Papain Family with a Long Propeptide Domain J. Biol. Chem., May 14, 1999; 274(20): 13800 - 13809. [Abstract] [Full Text] [PDF]

				I. Santamaria, G. Velasco, A. M. Pendas, A. Fueyo, and C. Lopez-Otin Cathepsin Z, a Novel Human Cysteine Proteinase with a Short Propeptide Domain and a Unique Chromosomal Location J. Biol. Chem., July 3, 1998; 273(27): 16816 - 16823. [Abstract] [Full Text] [PDF]