AIDS Laboratory - Infectious Diseases Unit

Topics of research

Our research focuses on 3'®5' exonuclease activity of tumor suppressor protein p53. 

1. The genetic heterogeneity of HIV, the causitive agent of AIDS, is responsible for a number of difficulties for control of viral disease and poses important problems for the design of new vaccines ant antiviral agents. Much of the genetic heterogeneity stems from the low fidelity of DNA synthesis of HIV reverse transcriptase. Our studies revealed that cytoplasmic p53 protein might provide the proofreading function for HIV reverse transcriptase.

2. Mitochondrial localization of p53 was observed in stressed and unstressed cells. p53 is involved in DNA repair and apoptosis. It exerts physical and functional interactions with mitochondrial DNA and DNA polymerase g. The exact role of p53 in mitochondria remains incomplete, since p53 may serve a triggering function for mitochondrial-driven apoptosis and mtDNA repair. Our results demonstrate that p53 in mitochondria may be a component of an error-repair pathway and serve as guardian of the mitochondrial genome.

3. The occurrence of pathologically stable mRNA of proto-oncogenes, growth factors and cyclins has been proposed  to contribute to experimental and human oncogenesis. The mRNA degradation is now recognized as an important regulatory step in controlling gene expression. The instability is regulated by cis-acting AU-rich elements (AREs), a broad family of sequences, found in the 3' untranslated region of the short-lived (labile) mRNAs, (e.g cyclins, proto-oncogenes). Our previous studies revealed that p53 in the cytoplasm, exerts high levels of 3¢® 5¢ exonuclease activity with various RNA substrates removing the 3'-terminal nucleotides, and RNA containing AU-rich sequences is the permissive substrate for exonucleolytic degradation. The fact that p53 is preferentially reactive with ARE-RNA points to the interesting possibility that p53, by facilitating ARE RNA degradation, might be implicated in ARE-mediated rapid mRNA destabilization in cytoplasm, which is important  for expression of proteins that control cell growth and/or apoptosis.

Current research directions in the lab include:

1. The studies on the influence of cytoplasmic proteins, p53 and HuR on the replication fidelity of HIV reverse transcriptase.

2. To elucidate p53 exonuclease activity in mitochondria under conditions that provoke p53-dependent apoptosis following the DNA damage.

3. To investigate the functional role of p53 in ARE-mediated mRNA destabilization in cytoplasm.

Available positions

We have available position for M.Sc and Ph.D students in our lab.