Truncated human cathepsin L, encoded by a novel splice variant, exhibits altered subcellular localization and cytotoxicity.
Cathepsin L (ctsl), a lysosomal cyteine protease over expressed and secreted by cancer cells, has been implicated in a number of physiological and pathological processes including tumor cell proliferation and metastasis. In the present study we demonstrate that an unknown mRNA of human origin (Gene Bank accession number AF 217997) is a splice variant of human cathepsin L mRNA (hCATL A IV) and encodes a truncated form of cathepsin L (Deltactsl) containing only 151 C-terminal amino acids. This isoform is cytotoxic to the mammalian cells. Transient transfection studies revealed that unlike ctsl, upon over expression in eukaryotic cells Deltactsl is not secreted in to the media. Immunogold electron microscopy exhibited its localization to nuclear, perinuclear and cytosolic region. In view of its cytotoxic property, targeted expression of Deltactsl in tumor cells may prove useful in the management of cancer.
Sansanwal
Poonam
P
Departments of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.
Shukla
Abhay A
AA
Das
Taposh K
TK
Chauhan
Shyam S
SS
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D056668:Cathepsin L / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D002467:Cell Nucleus / Q000201:enzymology / Q000648:ultrastructure; D002470:Cell Survival / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry; D015316:Genetic Therapy; D056945:Hep G2 Cells; D006801:Humans; D008247:Lysosomes / Q000648:ultrastructure; D051379:Mice; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D021381:Protein Transport; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment
D018076:DNA, Complementary; D020033:Protein Isoforms; D011994:Recombinant Proteins; C534281:CTSL protein, human; D056668:Cathepsin L