Imperial College London
Portrait Picture

Professor Guido Franzoso

Faculty of Medicine, Department of Immunology and Inflammation

Chair in Inflammation and Signal Transduction
 
 
 
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Contact

 

+44 (0)20 3313 8421g.franzoso Website

 
 
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Assistant

 

Miss Anjli Jagpal +44 (0)20 3313 3152

 
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Location

 

5N1Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Koh:2015:10.1172/JCI79134,
author = {Koh, CM and Khattar, E and Leow, SC and Liu, CY and Muller, J and Ang, WX and Li, Y and Franzoso, G and Li, S and Guccione, E and Tergaonkar, V},
doi = {10.1172/JCI79134},
journal = {Journal of Clinical Investigation},
pages = {2109--2122},
title = {Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity},
url = {http://dx.doi.org/10.1172/JCI79134},
volume = {125},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Constitutively active MYC and reactivated telomerase often coexist in cancers. While reactivation of telomerase is thought to be essential for replicative immortality, MYC, in conjunction with cofactors, confers several growth advantages to cancer cells. It is known that the reactivation of TERT, the catalytic subunit of telomerase, is limiting for reconstituting telomerase activity in tumors. However, while reactivation of TERT has been functionally linked to the acquisition of several “hallmarks of cancer” in tumors, the molecular mechanisms by which this occurs and whether these mechanisms are distinct from the role of telomerase on telomeres is not clear. Here, we demonstrated that first-generation TERT-null mice, unlike Terc-null mice, show delayed onset of MYC-induced lymphomagenesis. We further determined that TERT is a regulator of MYC stability in cancer. TERT stabilized MYC levels on chromatin, contributing to either activation or repression of its target genes. TERT regulated MYC ubiquitination and proteasomal degradation, and this effect of TERT was independent of its reverse transcriptase activity and role in telomere elongation. Based on these data, we conclude that reactivation of TERT, a direct transcriptional MYC target in tumors, provides a feed-forward mechanism to potentiate MYC-dependent oncogenesis.
AU  - Koh,CM
AU  - Khattar,E
AU  - Leow,SC
AU  - Liu,CY
AU  - Muller,J
AU  - Ang,WX
AU  - Li,Y
AU  - Franzoso,G
AU  - Li,S
AU  - Guccione,E
AU  - Tergaonkar,V
DO  - 10.1172/JCI79134
EP  - 2122
PY  - 2015///
SN  - 1558-8238
SP  - 2109
TI  - Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI79134
UR  - https://www.jci.org/articles/view/79134
UR  - http://hdl.handle.net/10044/1/25823
VL  - 125
ER  -
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