Role of the F-box protein Skp2 in lymphomagenesis

Citation
E. Latres et al., Role of the F-box protein Skp2 in lymphomagenesis, P NAS US, 98(5), 2001, pp. 2515-2520
Citations number
29
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
98
Issue
5
Year of publication
2001
Pages
2515 - 2520
Database
ISI
SICI code
0027-8424(20010227)98:5<2515:ROTFPS>2.0.ZU;2-F
Abstract
The F-box protein Skp2 (S-phase kinase-associated protein 2) positively reg ulates the G(1)-S transition by controlling the stability of several G(1) r egulators, such as the cell cycle inhibitor p27. We show here that Skp2 exp ression correlates directly with grade of malignancy and inversely with p27 levels in human lymphomas. To directly evaluate the potential of Skp2 to d eregulate growth in vivo, we generated transgenic mice expressing Skp2 targ eted to the T-lymphoid lineage as well as double transgenic mice coexpressi ng Skp2 and activated N-Ras. A strong cooperative effect between these two transgenes induced T cell lymphomas with shorter latency and higher penetra nce, leading to significantly decreased survival when compared with control and single transgenic animals. Furthermore, lymphomas of Nras single trans genic animals often expressed higher levels of endogenous Skp2 than tumors of double transgenic mice. This study provides evidence of a role for an F- box protein in oncogenesis and establishes SKP2 as a protooncogene causally involved in the pathogenesis of lymphomas.