Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cathepsin D (cath-D) gene, coding for a ubiquitous lysosomal aspartyl protease, is overexpressed in aggressive human breast cancers, and its transcription is induced by estrogens in hormone-responsive breast cancer cells. We have determined the structure and function of the proximal 5' upstream region of the human cath-D gene from MCF7 cells. We show that the promoter has a compound structure with features of both housekeeping genes (high G+C content and potential transcription factor Sp1 sites) and regulated genes (TATAA sequence). By RNase protection assay, we show that transcription is initiated at five major transcription sites (TSSI to -V) spanning 52 base pairs. In hormone-responsive breast cancer cells, estradiol increased by 6- to 10-fold the level of RNAs initiated at TSSI, which is located about 28 base pairs downstream from the TATA box. The specific regulation by estradiol of transcription starting at site I exclusively was confirmed by primer extension. Moreover, the same estradiol effect was observed in the ZR75-1 cell line and in MDA-MB231 estrogen-resistant breast cancer cells stably transfected with the estrogen receptor. Site-directed mutagenesis indicated that the TATA box is essential for initiation of cath-D gene transcription at TSSI. In breast cancer biopsy samples, high levels of TATA-dependent transcription were correlated with overexpression of cath-D mRNA. We conclude that cath-D behaves, depending on the conditions, as a housekeeping gene with multiple start sites or as a hormone-regulated gene that can be controlled from its TATA box.
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PMID:Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells. 841 24

In the fat body of insects with cyclic egg maturation, lysosomes play a critical role in the termination of vitellogenesis by selectively degrading the secretory machinery involved in the massive production of yolk protein precursors. To investigate this fat body-specific lysosomal activity in the mosquito, a cathepsin D-like aspartic protease (LAP) was previously purified and its cDNA cloned. Here we report the isolation of the AaLAP gene from an Aedes aegypti genomic library. The transcribed region of the gene is comprised of five exons, spanning 1904 base pairs. Restriction fragment length polymorphism (RFLP) and genomic clone analyses show this gene to be single copy and polymorphic. Primer extension analysis revealed two putative transcription start sites (TSS). The extension products corresponding to the distal and proximal TSSs were present in both pre- and vitellogenic fat bodies, suggesting that both TSSs are involved in housekeeping as well as tissue-specific expression of this gene. TATA box-like and arthropod initiator sequences, hallmarks of regulated genes, were present near each putative TSS. Several sequences resembling binding sites for liver- and fat body-specific transcription factors were identified within 1 kb upstream and downstream of the gene. Significantly, direct binding for the C/EBP and GATA families of transcription factors was demonstrated in vitro by electrophoretic mobility shift assays (EMSA). Three sequences located upstream of AaLAP resembled the Drosophila melanogaster yolk protein fat body enhancer (Dm Yp FBE). Potential hormone-response elements were also recognized in the gene; however, they did not bind the mosquito ecdysteroid receptor/Ultraspiracle heterodimer in EMSA experiments, indicating that these sequences may interact with different nuclear receptors.
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PMID:Analysis of the mosquito lysosomal aspartic protease gene: an insect housekeeping gene with fat body-enhanced expression. 913 12

The aim of this study was to establish a fasting-refeeding protocol to investigate the expression of growth-related genes during the transition between catabolic and anabolic states in Atlantic halibut (Hippoglossus hippoglossus L.). Juveniles of approximately 950 g were maintained at ambient temperature (5-8 degrees C) until the 1st of May, then fasted for two months and refed for two months at 7.7-8.0 degrees C under continuous low light. Fast epaxial myotomal muscle was sampled at -64 d (days), -38 d, 0 d (start of refeeding), 3 d, 7 d, 14 d, 30 d and 60 d. Average body mass was unchanged over the fasting period but increased by 24.4% following 60 d refeeding. qPCR was used to analyse the stability of expression of five potential reference genes (Eef2, Fau, 18SrRNA, Actb and Tubb2) with GeNorm and Normfinder. Expression of the growth-related genes, cathepsin B (ctsb), cathepsin D (ctsd), insulin-like growth factor-I and II (IGF-I and II) and insulin-like growth factor-I receptor 1a (IGF-IRa) was normalised using the geometric average of the two most stable housekeeping genes, Fau and 18SrRNA. IGF-I mRNA showed a transient 2.6-fold increase in abundance with refeeding at 7 d whilst transcripts for IGF-II and IGF-IRa were elevated during fasting and decreased 3.8-fold and 3-fold between the 0 d and 3 d samples respectively. Ctsb expression increased between -64 d and 0 d and then decreased approximately 10-fold by 14 d refeeding. In contrast, ctsd was relatively unaffected by the fasting-refeeding cycle, showing a modest (approximately 35%) transient decrease in expression between the 0 d and 30 d refeeding samples. It was concluded that the experimental protocol adopted and housekeeping genes identified were suitable for investigating the catabolic-anabolic transition in halibut skeletal muscle.
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PMID:Expression of growth-related genes in muscle during fasting and refeeding of juvenile Atlantic halibut, Hippoglossus hippoglossus L. 1883 58