Expression analysis and modulation by HIV-Tat of the tyrosine phosphatase HD-PTP.
The human immunodeficiency virus type 1 Tat transactivates viral proteins and also affects the expression of eukaryotic genes. Since Tat is angiogenic, we assumed that the isolation of differentially expressed genes in Tat-treated endothelial cells would yield insights into the molecular mechanisms of the angiogenic process. By RNA fingerprinting, we found that Tat upregulates the tyrosine phosphatase HD-PTP mRNA in a human endothelial cell line. At the moment, little is known about HD-PTP. We here show that HD-PTP is highly conserved through evolution from yeast to man, and is ubiquitously distributed in adult and fetal tissues. HD-PTP is expressed in human cell lines derived from different tumors, but the mRNA levels do not appear to correlate with the malignant phenotype of the cells. HD-PTP mRNA was also detected in cell lines derived from tumors that develop in BKV/Tat-transgenic mice. Interestingly, a relation exists between the amounts of secreted Tat and the levels of HD-PTP mRNA. HD-PTP encodes a 185-kDa protein which is expressed in human endothelial from the umbilical cord and in human Kaposi-spindle cells. Tat-induction of HD-PTP mRNA parallels only with a slight increase of the protein, which occurs after 24 and 48 h of incubation in the presence of Tat. These results suggest that HD-PTP amounts might be regulated both at the transcriptional and post-transcriptional levels.
Mariotti
Massimo
M
Department of Preclinical Sciences, University of Milan Medical School, Italy. massimo.mariotti@unimi.it
Castiglioni
Sara
S
Maier
Jeanette A M
JA
D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression; D015696:Gene Products, tat / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects / Q000378:metabolism*; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000378:metabolism*; D014018:Tissue Distribution; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D015696:Gene Products, tat; D012333:RNA, Messenger; C114102:PTPN23 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054558:Protein Tyrosine Phosphatases, Non-Receptor