Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts.
Transfection of an activated rat oncogene into NIH3T3 fibroblasts leads to transformation and induction of a metastatic phenotype. To identify genes whose activation might mediate these processes, we used a differential screening strategy. A 1.5-kb transcript is induced fiftyfold, constitutes 1% of ras transformed cell messenger RNA (mRNA) and is the most abundantly induced message in these cells. Our sequence data shows that it encodes murine cathepsin L, a potent collagenolytic and elastinolytic lysosomal enzyme. The murine clone was used to isolate human cathepsin L complementary DNA (cDNA) clones. The complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L are presented and compared to other papain family cysteine proteinases. Northern analysis shows that both human and murine cathepsin L probes hybridize to a 1.5-kb transcript in several tissues, but also to a 4-kb transcript in human kidney. These clones will facilitate studies of the structure, expression, and function of cathepsin L, including its unexpected upregulation in transformation.
Joseph
L J
LJ
Howard Hughes Medical Institute, Department of Medicine, University of Chicago, Illinois 60637.
Chang
L C
LC
Stamenkovich
D
D
Sukhatme
V P
VP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002403:Cathepsins / Q000235:genetics*; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D015246:Deoxyribonuclease EcoRI; D004792:Enzyme Precursors / Q000235:genetics*; D005347:Fibroblasts; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014170:Transformation, Genetic
D004792:Enzyme Precursors; D012333:RNA, Messenger; D004247:DNA; D004262:DNA Restriction Enzymes; D015246:Deoxyribonuclease EcoRI; D002403:Cathepsins; C055808:preprocathepsin L