# Antagonistic effect of the tumor suppressor Menin and the HBZ protein of HTLV-1 on telomerase activity

Anne-Sophie Kuhlmann, Sophie Girard, Louis Gazzolo, Madeleine Duc Dodon

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Anne-Sophie Kuhlmann, Sophie Girard, Louis Gazzolo, Madeleine Duc Dodon. Antagonistic effect of the tumor suppressor Menin and the HBZ protein of HTLV-1 on telomerase activity. Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts, Sep 2009, Montpellier, France. pp.P33, 10.1186/1742-4690-6-S2-P33. inserm-00663601

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# Antagonistic effect of the tumor suppressor Menin and the HBZ protein of HTLV-1 on telomerase activity

Anne-Sophie Kuhlmann*¹,²,³, Sophie Girard²,³, Louis Gazzolo¹,²,³ and
Madeleine Duc Dodon¹,²,³

Address: ¹Virologie Humaine, INSERM-U758, 69364 Lyon Cedex 07, France, ²Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France and ³IFR 128 BioSciences Lyon-Gerland, 69364 Lyon Cedex 07, France

from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts
Montpellier, France. 21-23 September 2009

Published: 24 September 2009

Retrovirology 2009, 6(Suppl 2):P33 doi:10.1186/1742-4690-6-S2-P33

This abstract is available from: http://www.retrovirology.com/content/6/S2/P33

© 2009 Kuhlmann et al; licensee BioMed Central Ltd.

## Background

HTLV-1 is a retrovirus responsible for adult T-cell leuke-
mia (ATL) in 5% of infected people. ATL is characterised
by a monoclonal proliferation of infected CD4+ T lym-
phocytes in which a high telomerase activity associated to
a poor prognosis has been observed [1]. Furthermore,
HBZ is the only viral protein clearly detectable in all ATL
patient samples. This protein has been shown to up-regu-
late the transcription of the catalytic subunit of telomer-
ase, hTERT. Therefore interaction of HBZ with AP-1
transcription factor JunD on the proximal promoter of
hTERT is required to up-regulate the gene [2].

Menin, a tumor suppressor, is known as a repressor of both JunD transcriptional activity [3] and hTERT transcription [4]. These data led us to investigate the mechanisms underlying hTERT up-regulation by HBZ and JunD in the presence of Menin.

## Results

Thus we have shown that HBZ is able to counteract the
inhibitory effect exerted by Menin on JunD transcrip-
tional activity in a dose dependent manner. HBZ is also
able to partially restore endogenous telomerase activity in
spite of the Menin presence. HBZ and JunD have been
shown to co-immunoprecipitate with Menin protein sug-
gesting that HBZ does not counteract Menin by evicting it
from the complex. Menin repress JunD transcriptional
activity through the recruitment of histone deacetylases

whereas HBZ interacts with p300, an histone acetyl trans-
ferase. Thus we have demonstrated that p300 recruitment
by HBZ is necessary to stimulate JunD transcriptional
activity and hTERT proximal promoter in the presence of
Menin.

Similarly to hTERT and JunD which are highly expressed
in ATL cells, Menin mRNA are clearly detectable in pri-
mary ATL cells underlying the importance for HBZ to be
able to counteract the repression exerted by this tumor
suppressor.

## Conclusion

Our findings provide further insights in the the mecha-
nism of hTERT up-regulation by JunD and HBZ and ascer-
tain Menin as a new player in the ATL leukemogenic
process.

## References

1. Kubuki Y, Suzuki M, Sasaki H, Toyama T, Yamashita K, Maeda K, Ido A, Matsuoka H, Okayama A, Nakanishi T, Tsubouchi H: *Leuk Lym-phoma* 2005, **46**:393-9.

2. Kuhlmann AS, Villaudy J, Gazzolo L, Castellazzi M, Mesnard JM, Duc Dodon M: *Retrovirology* 2007, **4**:92.

3. Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, Saggar S, Chandrasekharappa SC, Collins FS, Spiegel AM, Marx SJ, Burns AL: *Cell* 1999, **96**:143-52.

4. Lin SY, Elledge SJ: *Cell* 2003, **113**:881-9.

<footnote>* Corresponding author</footnote>