P130 IS DISPENSABLE IN PERIPHERAL T-LYMPHOCYTES - EVIDENCE FOR FUNCTIONAL COMPENSATION BY P107 AND PRB

The proteins encoded by the retinoblastoma gene family, pRB, p107, and p130, have been implicated in the regulation of cellular proliferatio n, differentiation, and transformation. Because interactions between p 130 and E2F transcription factors have been proposed to play a role in the establishment and/or maintenance of quiescence in human periphera l T lymphocytes, we examined lymphoid differentiation and proliferatio n in p130-deficient mice. We show that p130 T cells proliferate normal ly in culture and exhibit normal cellmediated immune function in vivo. However, p130(-/-)T lymphocytes expressed elevated levels of p107, an d the characteristic p130-E2F DNA binding complex was replaced by a p1 07-E2F complex. Adoptive transfer of fetal liver lymphoid progenitors allowed us to circumvent the neonatal lethality associated with loss o f p130 and p107 and to analyze the phenotype of p130(-/-);p107(-/-) pe ripheral T lymphocytes. These cells achieved a quiescent state, exhibi ted derepression of a subset of E2F target genes, and were hypersensit ive to concanavalin A stimulation. Interestingly, a significant portio n of the E2F-4 in p130(-/-);p107(-/-)T cells was detected in a complex with pRB and an as-yet-unidentified protein. These findings provide a biochemical basis for functional compensation between pRB family prot eins.