We are investigating the effect of Tat on homeodomain protein heterodimerization and DNA binding. Future studies will determine the target genes of the homeodomain transcription factors. Increasing evidence supports a role for homeodomain proteins in differentiation processes that occur in adults. The homeodomain proteins have been implicated in the proliferation of hematopoetic precursor cells in response to growth factors, and in their differentiation to mature erythrocytes and leukocytes. We propose that some aspects of HIV induced immunodeficiency are mediated by Tat interference with homeodomain function during development of lymphocytes or in their proliferation in response to infection.
Current studies address the biological significance of the Tat-homeodomain protein interaction.
HIV positive individuals have a high incidence of non-Hodgkin's T cell lymphoma, and homeodomain genes have been implicated in acute myelocytic and lymphocytic leukemia. Brown, J. A., T. K. Howcroft, and D. S. Singer.