Mecanismos moleculares da transformação maligna mediada pelo antígeno MT do vírus polioma

Author(s)

Sheila Maria Brochado

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2001-02-22

Examining board members

Mari Cleide Sogayar; Pio Colepicolo Neto; Eugenia Costanzi Strauss

• Advisor: Mari Cleide Sogayar

Abstract

Polyomavirus is a DNA tumor virus that induces a variety of tumors in mice. Its genome encodes three proteins, namely, Large T, Middle T and Small T antigens, which have been implicated in cell transformation. The MT oncoprotein plays an essential role in cell transformation by binding to and activating several cytoplasmic proteins that participate in growth factorsinduced mitogenic signal transduction to the nucleus. We have previously reported that the AP-1 transcriptional complex is a target for MT during cell transformation, but AP-1 activation does not seem to be sufficient for cell transformation. Here, we have analyzed the requirement for AP-1 activation and the role of the low molecular weight acid phosphatase protein (LMW-PTP) in MT-induced cell transformation. Overexpression of a dominant-negative cJun mutant in MT transformed cells, led to morphological alterations (cell flattening) and inhibition of cell growth in agarose suspension. Analysis of the low molecular weight acid phosphatase protein in MT transformed cells showed a decrease in the specific activity of this enzyme, but gene expression was not altered at the transcriptional level. The results obtained suggest that the AP-1 complex is necessary for cell transformation induced by MT and indicate the involvement of the low molecular weight acid phosphatase protein in this process. (AU)