Transcription of Human Cathepsin B Is Mediated by Sp1 and Ets Family Factors in Glioma

Yan, Shiqing; Berquin, Isabelle M.; Troen, Bruce R.; Sloane, Bonnie F.
February 2000
DNA & Cell Biology;Feb2000, Vol. 19 Issue 2, p79
Academic Journal
Cathepsin B expression is increased at both the mRNA and protein levels in a wide variety of tumors. The mechanisms responsible for this regulation are not well elucidated. We have isolated a 2.2-kb cathepsin B genomic fragment that contains the 5' -flanking region of the cathepsin B gene. Using reporter gene analysis in human glioblastoma U87MG cells, we have mapped a 228-bp fragment (-172 to +56) having high promoter activity. This promoter region has a high G+C content; contains potential Sp1, Ets, and USF binding motifs; and lacks canonical TATA and CAAT boxes immediately upstream of the major transcriptional initiation site. Cotransfection experiments demonstrated that Sp1 and Ets1 could trans-activate cathepsin B transcription, whereas Ets2 could not. Electrophoretic mobility shift assays and supershift assays revealed that three of the four putative Sp1 sites in this promoter region form a specific complex containing the Sp1 transcription factor. Mutating all four of the Sp1 binding sites individually markedly reduced the promoter activity of transfected reporter genes in U87 cells. Cotransfection of this cathepsin B promoter construct with Sp1 family expression vectors in Schneider's Drosophila line 2 (SL2) cells demonstrated that Sp1 and Sp3, but not Sp4, activated cathepsin B transcription. Taken together, these results suggest that Sp1, Sp3, and Ets1 are important factors in cathepsin B transcription. The regulation of cathepsin B transcription by Sp1- and Sp1- related factors is mediated through multiple GC boxes.


Related Articles

  • In vivo inhibition of cysteine proteinases delays the onset of growth of human pancreatic cancer explants. Van Noorden, C J F; Jonges, T G N; Meade-Tollin, L C; Smith, R E; Koehler, A // British Journal of Cancer;2/15/2000, Vol. 82 Issue 4, p931 

    An animal model was used to study the effects of oral treatment with a small molecular selective inhibitor of cysteine proteinases, Z-Phe-Arg-fluoromethylketone (Z-Phe-Arg-FMK) on primary tumour development. Poorly differentiated rapidly growing and moderately differentiated slowly growing human...

  • Caspase activation is not death. Perfettini, Jean-Luc; Kroemer, Guido // Nature Immunology;Apr2003, Vol. 4 Issue 4, p308 

    Reports that the inhibition of caspase, a family of cysteine proteases facilitates the death of tumor necrosis factor indicating that caspase activation does not signify apoptotic death of cells. Study of Caenorhabditis elegans that indicates the importance of caspse activation for apoptotic...

  • Compartmentation of Nrf-2 Redox Control: Regulation of Cytoplasmic Activation by Glutathione and DNA Binding by Thioredoxin-1. Hansen, Jason M.; Watson, Walter H.; Jones, Dean P. // Toxicological Sciences;Nov2004, Vol. 82 Issue 1, p308 

    Nrf-2 is a redox-sensitive transcription factor that is activated by an oxidative signal in the cytoplasm but has a critical cysteine that must be reduced to bind to DNA in the nucleus. The glutathione (GSH) and thioredoxin (TRX) systems have overlapping functions in thiol/disulfide redox...

  • Cloning and characterization of a novel cysteine protease gene (HbCP1) from Hevea brasiliensis. Shi-Qing Peng; Jia-Hong Zhu; Hui-Liang Li; Wei-Min Tian // Journal of Biosciences;Dec2008, Vol. 33 Issue 5, p681 

    The full-length cDNA encoding a cysteine protease, designated HbCP1, was isolated for the first time from Hevea brasiliensis by the rapid amplification of cDNA ends (RACE) method. HbCP1 contained a 1371 bp open reading frame encoding 457 amino acids. The deduced HbCP1 protein, which showed high...

  • Sparcs turn into flames. Novak, Kristine // Nature Reviews Cancer;Jan2004, Vol. 4 Issue 1, p8 

    Reports on findings of Sangaletti and colleagues' study which showed that stromal cells produce a secreted protein, acidic and rich in cysteine, Sparc, that helps organize the basement-membrane structure that is required for tumour progression. Role of Sparc in tissue repair and remodeling;...

  • DREB2C acts as a transcriptional activator of the thermo tolerance-related phytocystatin 4 ( AtCYS4) gene. Je, Jihyun; Song, Chieun; Hwang, Jung; Chung, Woo; Lim, Chae // Transgenic Research;Feb2014, Vol. 23 Issue 1, p109 

    Phytocystatins are proteinaceous inhibitors of cysteine proteases. They have been implicated in the regulation of plant protein turnover and in defense against pathogens and insects. Here, we have characterized an Arabidopsis phytocystatin family gene, Arabidopsis thaliana phytocystatin 4 (...

  • Screening of an oligopeptide antagonist for interleukin-6 from a random phage library. Mizuguchi, Hiroshi; Kubomi, Tomoko; Nomura, Rina; Yasukawa, Kiyoshi; Imanaka, Tadayuki; Takagi, Masahiro // Biotechnology Letters;Jun2000, Vol. 22 Issue 12, p1015 

    To develop a small peptide antagonist for a cytokine, an oligopeptide ligand interacting with interleukin-6 (IL-6) has been screened by affinity panning from a random heptapeptide displaying phage library. After biopanning five times against IL-6, ten phages displaying heptapeptides with...

  • Characterization of human gene locus CYYR1: a complex multi-transcript system. Casadei, Raffaella; Pelleri, Maria; Vitale, Lorenza; Facchin, Federica; Canaider, Silvia; Strippoli, Pierluigi; Vian, Matteo; Piovesan, Allison; Bianconi, Eva; Mariani, Elisa; Piva, Francesco; Frabetti, Flavia // Molecular Biology Reports;Sep2014, Vol. 41 Issue 9, p6025 

    Cysteine/tyrosine-rich 1 ( CYYR1) is a gene we previously identified on human chromosome 21 starting from an in-depth bioinformatics analysis of chromosome 21 segment 40/105 (21q21.3), where no coding region had previously been predicted. CYYR1 was initially characterized as a four-exon gene,...

  • PINCH expression and its significance in esophageal squamous cell carcinoma. Zhu, Zhenlong; Yang, Yanhong; Zhang, Yu; Wang, Zhengmin; Cui, Dongsheng; Zhang, Jinting; Wang, Mingwei; Sun, Xiao-Feng // Disease Markers;2008, Vol. 25 Issue 2, p75 

    Particularly interesting new cysteine-histidine rich protein (PINCH), as a newly discovered protein of LIM family members, may play a role in signal transduction of integrin and growth factor, and involved in the incidence and development of tumors. PINCH protein is overexpressed in...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics