Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 15 June 2010
Vol. 3, Issue 126, p. ra47
[DOI: 10.1126/scisignal.2000681]


Ablation of the Kinase NDR1 Predisposes Mice to the Development of T Cell Lymphoma

Hauke Cornils1*, Mario R. Stegert1, Alexander Hergovich1, Debby Hynx1, Debora Schmitz1, Stephan Dirnhofer2, and Brian A. Hemmings1*

1 Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
2 Institute of Pathology, University of Basel, Schönbeinstrasse 40, CH-4003 Basel, Switzerland.

Abstract: Defective apoptosis contributes to the development of various human malignancies. The kinases nuclear Dbf2–related 1 (NDR1) and NDR2 mediate apoptosis downstream of the tumor suppressor proteins RASSF1A (Ras association domain family member 1A) and MST1 (mammalian Ste20-like kinase 1). To further analyze the role of NDR1 in apoptosis, we generated NDR1-deficient mice. Although NDR1 is activated by both intrinsic and extrinsic proapoptotic stimuli, which indicates a role for NDR1 in regulating apoptosis, NDR1-deficient T cells underwent apoptosis in a manner similar to that of wild-type cells in response to different proapoptotic stimuli. Analysis of the abundances of NDR1 and NDR2 proteins revealed that loss of NDR1 was functionally compensated for by an increase in the abundance of NDR2 protein. Despite this compensation, NDR1–/– and NDR1+/– mice were more prone to the development of T cell lymphomas than were wild-type mice. Tumor development in mice and humans was accompanied by a decrease in the overall amounts of NDR proteins in T cell lymphoma samples. Thus, reduction in the abundance of NDR1 triggered a decrease in the total amount of both isoforms. Together, our data suggest that a reduction in the abundances of the NDR proteins results in defective responses to proapoptotic stimuli, thereby facilitating the development of tumors.

* To whom correspondence should be addressed. E-mail: hauke.cornils{at} (H.C.); brian.hemmings{at} (B.A.H.)

Citation: H. Cornils, M. R. Stegert, A. Hergovich, D. Hynx, D. Schmitz, S. Dirnhofer, B. A. Hemmings, Ablation of the Kinase NDR1 Predisposes Mice to the Development of T Cell Lymphoma. Sci. Signal. 3, ra47 (2010).

Read the Full Text

NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15.
S. Chiba, Y. Amagai, Y. Homma, M. Fukuda, and K. Mizuno (2013)
EMBO J. 32, 874-885
   Abstract »    Full Text »    PDF »
Mammalian Sterile 20-like Kinase 1 Suppresses Lymphoma Development by Promoting Faithful Chromosome Segregation.
T.-S. Kim, D.-H. Lee, S. K. Kim, S. Y. Shin, E.-J. Seo, and D.-S. Lim (2012)
Cancer Res. 72, 5386-5395
   Abstract »    Full Text »    PDF »
MICAL-1 Is a Negative Regulator of MST-NDR Kinase Signaling and Apoptosis.
Y. Zhou, Y. Adolfs, W. W. M. P. Pijnappel, S. J. Fuller, R. C. Van der Schors, K. W. Li, P. H. Sugden, A. B. Smit, A. Hergovich, and R. J. Pasterkamp (2011)
Mol. Cell. Biol. 31, 3603-3615
   Abstract »    Full Text »    PDF »
The growing role of the Hippo-NDR kinase signalling in neuronal development and disease.
K. Emoto (2011)
J. Biochem. 150, 133-141
   Abstract »    Full Text »    PDF »
Human NDR Kinases Control G1/S Cell Cycle Transition by Directly Regulating p21 Stability.
H. Cornils, R. S. Kohler, A. Hergovich, and B. A. Hemmings (2011)
Mol. Cell. Biol. 31, 1382-1395
   Abstract »    Full Text »    PDF »
Mammalian Hippo pathway: from development to cancer and beyond.
Y. Bao, Y. Hata, M. Ikeda, and K. Withanage (2011)
J. Biochem. 149, 361-379
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882