|
|
Blood, 19 February 2009, Vol. 113, No. 8, pp. 1689-1698.
Prepublished online as a Blood First Edition Paper on November 10, 2008; DOI 10.1182/blood-2008-03-147967.
 Previous Article | Next Article 
Submitted March 28, 2008
Accepted October 23, 2008
Notch signaling mediates G1/S cell cycle progression in T cells via cyclin D3 and its dependent kinases
Ila Joshi, Lisa M Minter, Janice Telfer, Renee M Demarest, Anthony J. Capobianco, Jon C. Aster, Piotr Sicinski, Abdul Fauq, Todd E Golde, and Barbara A Osborne*
Program in Molecular and Cell Biology, University of Massachusetts, Amherst, MA, United States
Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, MA, United States
Molecular and Cellular Oncogenesis, The Wistar Institute, Philadelphia, PA, United States
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
Department of Cancer Biology, Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, United States
* Corresponding author; email: osborne{at}vasci.umass.edu.
Notch signaling plays a role in normal lymphocyte development and function. Activating Notch1-mutations, leading to aberrant downstream signaling, have been identified in human T-cell acute lymphoblastic leukemia (T-ALL). While this highlights the contribution of Notch signaling to T-ALL pathogenesis, the mechanisms by which Notch regulates proliferation and survival in normal and leukemic T cells are not fully understood. Our findings identify a role for Notch signaling in G1-S progression of cell cycle in T cells. Here we show expression of the G1 proteins, cyclin D3, CDK4 and CDK6, is Notch-dependent both in vitro and in vivo, and we outline a possible mechanism for the regulated expression of cyclin D3 in activated T cells via CSL, as well as a non-canonical Notch signaling pathway. While cyclin D3 expression contributes to cell cycle progression in Notch-dependent human T-ALL cell lines, ectopic expression of CDK4 or CDK6 together with cyclin D3 shows partial rescue from  -secretase inhibitor- (GSI) induced G1 arrest in these cell lines. Importantly, cyclin D3 and CDK4 are highly overexpressed in Notch-dependent T-cell lymphomas, justifying the combined use of cell cycle inhibitors and GSI in treating human T-cell malignancies.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Another Notch on the belt
- Lynn M. Schnapp
Blood 2009 113: 1615-1616.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
L. FU, K.-I. KATSUBE, and S. TOHDA
Transition of Cleaved Notch1 and Gene Expression Changes in Myeloblastic Leukemia Cells Stimulated with Notch Ligands
Anticancer Res,
October 1, 2009;
29(10):
3967 - 3970.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Wang, J. Rud, C. M. Olson Jr., J. Anguita, and B. A. Osborne
Phosphorylation of Nur77 by the MEK-ERK-RSK Cascade Induces Mitochondrial Translocation and Apoptosis in T Cells
J. Immunol.,
September 1, 2009;
183(5):
3268 - 3277.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Schnapp
Another Notch on the belt
Blood,
February 19, 2009;
113(8):
1615 - 1616.
[Full Text]
[PDF]
|
|
|
|
|
