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 proliferation, differentiation, and transformation. Because interactions between p130 and E2F transcription factors have been proposed to play a role in the establishment and/or maintenance of quiescence in human peripheral T lymphocytes, we examined lymphoid differentiation and proliferation in p130-deficient mice. We show that p130-/- T cells proliferate normally in culture and exhibit normal cell-mediated immune function in vivo. However, p130-/- T lymphocytes expressed elevated levels of p107, and the characteristic p130-E2F DNA binding complex was replaced by a p107-E2F complex. Adoptive transfer of fetal liver lymphoid progenitors allowed us to circumvent the neonatal lethality associated with loss of p130 and p107 and to analyze the phenotype of p130-/-;p107-/- peripheral T lymphocytes. These cells achieved a quiescent state, exhibited derepression of a subset of E2F target genes, and were hypersensitive to concanavalin A stimulation. Interestingly, a significant portion 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 proteins.
Mulligan
G J
GJ
Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA.
Wong
J
J
Jacks
T
T
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics; D011506:Proteins; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130