Transcriptional Activity of Plasmodium Subtilisin-like Protease 2 (Pf-Sub2) 5'Untranslated Regions and Its Interaction with Hepatocyte Growth Factor

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors and individual host responses to these determinants. In both humans and mice, liver injury is involved after parasite entry, which persists until the erythrocyte stage after infection with the fatal strain Plasmodium falciparum (Pf). Hepatocyte growth factor (HGF) has strong anti-apoptotic effects in various kinds of cells, and also has diverse metabolic functions. In this work, Pf-subtilisin-like protease 2 (Pf-Sub2) 5'untranslated region (UTR) was analyzed and its transcriptional activity was estimated by luciferase expression. Fourteen TATA boxes were observed but only one Oct-1 and c-Myb were done. In addition, host HGF interaction with Pf-Sub2 was evaluated by co-transfection of HGF- and Pf-Sub2-cloned vector. Interestingly, -1,422/+12 UTR exhibited the strongest luciferase activity but -329 to +12 UTR did not exhibit luciferase activity. Moreover, as compared with the control of unexpressed HGF, the HGF protein suppressed luciferase expression driven by the 5'untranslated region of the Pf-Sub2 promoter. Taken together, it is suggested that HGF controls and interacts with the promoter region of the Pf-Sub2 gene.

[1]  M. Zibaei,et al.  Experimental Toxocara cati Infection in Gerbils and Rats , 2010, The Korean journal of parasitology.

[2]  Seung-Young Yu,et al.  Suppression of CD4+ T-Cells in the Spleen of Mice Infected with Toxoplasma gondii KI-1 Tachyzoites , 2010, The Korean journal of parasitology.

[3]  R. Bucala,et al.  Toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host. , 2007, The Journal of infectious diseases.

[4]  Paul Garside,et al.  Malaria Impairs T Cell Clustering and Immune Priming despite Normal Signal 1 from Dendritic Cells , 2007, PLoS pathogens.

[5]  W. Tham,et al.  Transcription and coregulation of multigene families in Plasmodium falciparum. , 2007, Trends in parasitology.

[6]  Todd M. Gierahn,et al.  Regulatory motifs uncovered among gene expression clusters in Plasmodium falciparum. , 2007, Molecular and biochemical parasitology.

[7]  P. Gros,et al.  Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus , 2007, The Journal of experimental medicine.

[8]  S. Kappe,et al.  A clash to conquer: the malaria parasite liver infection , 2006, Molecular microbiology.

[9]  Ana Rodriguez,et al.  The silent path to thousands of merozoites: the Plasmodium liver stage , 2006, Nature Reviews Microbiology.

[10]  S. Howell,et al.  Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite , 2006, The Journal of cell biology.

[11]  A. Olivieri,et al.  Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage‐specific expression , 2006, Molecular microbiology.

[12]  C. Janse,et al.  Plasmodium post-genomics: better the bug you know? , 2006, Nature Reviews Microbiology.

[13]  L. Rénia,et al.  Liver-stage development of Plasmodium falciparum, in a humanized mouse model. , 2006, The Journal of infectious diseases.

[14]  A. Cowman,et al.  A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria , 2006, Nature.

[15]  M. Huynen,et al.  Combinatorial gene regulation in Plasmodium falciparum. , 2006, Trends in genetics : TIG.

[16]  C. Withers-Martinez,et al.  Molecular Identification of a Malaria Merozoite Surface Sheddase , 2005, PLoS pathogens.

[17]  Félix Recillas-Targa,et al.  Recombinant and native Plasmodium falciparum TATA-binding-protein binds to a specific TATA box element in promoter regions. , 2005, Molecular and biochemical parasitology.

[18]  C. Janse,et al.  Gene targeting demonstrates that the Plasmodium berghei subtilisin PbSUB2 is essential for red cell invasion and reveals spontaneous genetic recombination events , 2004, Cellular microbiology.

[19]  Simona Corso,et al.  Hepatocyte growth factor and its receptor are required for malaria infection , 2003, Nature Medicine.

[20]  T. Wellems,et al.  Plasmodium falciparum var Genes Are Regulated by Two Regions with Separate Promoters, One Upstream of the Coding Region and a Second within the Intron* , 2003, Journal of Biological Chemistry.

[21]  D. Wirth,et al.  Mapping of the Plasmodium falciparum multidrug resistance gene 5′‐upstream region, and evidence of induction of transcript levels by antimalarial drugs in chloroquine sensitive parasites , 2003, Molecular microbiology.

[22]  A. Cowman,et al.  Characterisation of the merozoite surface protein-2 promoter using stable and transient transfection in Plasmodium falciparum. , 2003, Molecular and biochemical parasitology.

[23]  S. Howell,et al.  A Single Malaria Merozoite Serine Protease Mediates Shedding of Multiple Surface Proteins by Juxtamembrane Cleavage* , 2003, Journal of Biological Chemistry.

[24]  P. Gros,et al.  Complex genetic control of susceptibility to malaria in mice , 2002, Genes and Immunity.

[25]  S. Akira,et al.  Plasmodium berghei Infection in Mice Induces Liver Injury by an IL-12- and Toll-Like Receptor/Myeloid Differentiation Factor 88-Dependent Mechanism1 , 2001, The Journal of Immunology.

[26]  M. Mota,et al.  Migration of Plasmodium sporozoites through cells before infection. , 2001, Science.

[27]  W. Nahorski,et al.  Liver injury in the course of malaria. , 2000, International maritime health.

[28]  R. Burt Genetics of host response to malaria. , 1999, International journal for parasitology.

[29]  H. Nariuchi,et al.  A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection. , 1998, Journal of immunology.

[30]  G. V. Vande Woude,et al.  Autocrine hepatocyte growth factor/scatter factor-Met signaling induces transformation and the invasive/metastastic phenotype in C127 cells. , 1996, Oncogene.

[31]  A. Cowman,et al.  Characterization of promoters and stable transfection by homologous and nonhomologous recombination in Plasmodium falciparum. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[32]  F. Chisari,et al.  Hepatitis B virus immunopathogenesis. , 1995, Annual review of immunology.

[33]  G. V. Vande Woude,et al.  Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Ravetch,et al.  Plasmodium: control of gene expression in malaria parasites. , 1993, Experimental parasitology.

[35]  Y. Joshi,et al.  Acute hepatic failure due to Plasmodium falciparum liver injury. , 2008, Liver.