Abstract:
:The F-box protein Skp2 (S-phase kinase-associated protein 2) positively regulates the G(1)-S transition by controlling the stability of several G(1) regulators, such as the cell cycle inhibitor p27. We show here that Skp2 expression correlates directly with grade of malignancy and inversely with p27 levels in human lymphomas. To directly evaluate the potential of Skp2 to deregulate growth in vivo, we generated transgenic mice expressing Skp2 targeted to the T-lymphoid lineage as well as double transgenic mice coexpressing Skp2 and activated N-Ras. A strong cooperative effect between these two transgenes induced T cell lymphomas with shorter latency and higher penetrance, leading to significantly decreased survival when compared with control and single transgenic animals. Furthermore, lymphomas of Nras single transgenic 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Latres E,Chiarle R,Schulman BA,Pavletich NP,Pellicer A,Inghirami G,Pagano Mdoi
10.1073/pnas.041475098keywords:
subject
Has Abstractpub_date
2001-02-27 00:00:00pages
2515-20issue
5eissn
0027-8424issn
1091-6490pii
041475098journal_volume
98pub_type
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