Identification of Jun dimerisation protein 2 (JDP2) as a novel cellular target of the Human T-cell Leukaemia Virus type 1 Tax oncoprotein


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Claire Walsh, Lynne Hampson, Anthony W. Oliver, Henry C. Kitchener, Ian N. Hampson

University of Manchester Gynaecological Oncology, School of Cancer Studies, Manchester, UK

Abstract

Background

Human T-cell leukaemia virus type 1 (HTLV-1) is the causative agent of Adult T-cell leukaemia (ATL), an aggressive haematological malignancy with poor prognosis. The HTLV-1 Tax oncoprotein is known to deregulate numerous cellular pathways that can lead to cellular transformation and although some of these effects are known, many await identification.

Method

Yeast two-hybrid screening was carried out with full-length Tax against a unique in-house normalised cDNA fragment library. Full length coding sequences of prospective Tax binding proteins were amplified and interactions confirmed by mammalian two hybrid.

Results

Jun dimerisation protein 2 (JDP2) was identified as a novel binding partner of Tax and this interaction was confirmed with full length JDP2 in mammalian cells.

Conclusion

JDP2 is an AP-1 transcription factor repressor protein, thought to have a role as both a tumour suppressor and a cellular survival protein. As AP-1 has been found to be constitutively active in ATL cells, we hypothesise that Tax could bind to JDP2 and block its function as an AP-1 repressor. This would promote constitutive activation of AP-1 transcription, which may contribute to increased cellular proliferation and transformation. We are currently testing this hypothesis using dominant negative JDP2 fragments combined with AP-1 site transcription reporter assays.

References

1. Heinrich, R., et al. (2004). J. Biol. Chem., 279, 5708–5715.

2. Lerdrup, M., et al. (2005). Biochim. Biophys. Acta., 1745, 29–37.

3. Mori, N., et al. (2000). Blood, 95, 3915-3921.

Background

Human T-cell leukaemia virus type 1 (HTLV-1) is the causative agent of Adult T-cell leukaemia (ATL), an aggressive haematological malignancy with poor prognosis. The HTLV-1 Tax oncoprotein is known to deregulate numerous cellular pathways that can lead to cellular transformation and although some of these effects are known, many await identification.

Method

Yeast two-hybrid screening was carried out with full-length Tax against a unique in-house normalised cDNA fragment library. Full length coding sequences of prospective Tax binding proteins were amplified and interactions confirmed by mammalian two hybrid.

Results

Jun dimerisation protein 2 (JDP2) was identified as a novel binding partner of Tax and this interaction was confirmed with full length JDP2 in mammalian cells.

Conclusion

JDP2 is an AP-1 transcription factor repressor protein, thought to have a role as both a tumour suppressor and a cellular survival protein. As AP-1 has been found to be constitutively active in ATL cells, we hypothesise that Tax could bind to JDP2 and block its function as an AP-1 repressor. This would promote constitutive activation of AP-1 transcription, which may contribute to increased cellular proliferation and transformation. We are currently testing this hypothesis using dominant negative JDP2 fragments combined with AP-1 site transcription reporter assays.

References

1. Heinrich, R., et al. (2004). J. Biol. Chem., 279, 5708–5715.

2. Lerdrup, M., et al. (2005). Biochim. Biophys. Acta., 1745, 29–37.

3. Mori, N., et al. (2000). Blood, 95, 3915-3921.