Naslov
Evidence for Different Mechanisms of Growth Inhibition of T-cell Lymphoma by Phorbol Esters and Concanavalin A

Autori
Desrivieres, Sylvane ; Volarević, Siniša ; Merčep, Luka ; Ferrari, Stefano

Izvornik
The Journal of biological chemistry (0021-9258) 272 (1997); 2470-2476

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cell growth; cell cycle; PMA; ConA; T-cell lymphoma

Sažetak
Stimuli that are mitogenic for mature T-cells induce cell cycle arrest in some T-cell tumors and T-cell hybridomas. The molecular mechanism of this growth inhibition is poorly understood. In this report, we show that in EL4, a murine T-lymphoma cell line, stimulation with concanavalin A or treatment with phorbol 13-myristate 12-acetate (PMA) inhibit growth, due to cell cycle arrest at both the G1 and the G2/M phases. The block at the G1 phase is accompanied by the appearance of a hypophosphorylated form of the retinoblastoma protein (pRb), due to the inhibition of G1 cyclin-Cdk complexes. However, the molecular mechanisms leading to this G1 cell cycle arrest differ between concanavalin A and PMA: concanavalin A inhibits both cyclin E-Cdk2 and cyclin D-Cdk4 complexes, while PMA inhibits only cyclin E-Cdk2. We demonstrate that concanavalin A inhibits cyclin D-Cdk4 activity by decreasing the amount of cyclin D. The inhibition of cyclin E-Cdk2 by both concanavalin A and PMA is due to increased binding of the Cdk inhibitor p21 to this complex. However, while stimulation of the cells with concanavalin A did not result in an evident increase of the total level of p21, treatment of the cells with PMA increased p21 levels significantly. Our results indicate, furthermore, that the G2/M block results from the inhibition of cyclin A- and cyclin B1-associated kinase activities. As for cyclin E-Cdk2, the inhibition of the cyclin A-Cdk2 complex is due to increased binding of the p21 inhibitor.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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