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PMID: 9418868 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

p130 is dispensable in peripheral T lymphocytes: evidence for functional compensation by p107 and pRB.

Molecular and cellular biology ·Vol. 18 ·No. 1 ·1998-01-00 ·Pages 206-20

Mulligan GJ, Wong J, Jacks T

Abstract

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.

MeSH Terms
Animals Cells, Cultured Gene Expression Regulation Humans Lymphocyte Activation/genetics Mice Mice, Mutant Strains Nuclear Proteins/genetics,metabolism Phosphoproteins/deficiency,genetics Proteins Retinoblastoma Protein/genetics,metabolism Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130 T-Lymphocytes/immunology,metabolism
Chemicals
Nuclear Proteins Phosphoproteins Proteins RBL1 protein, human RBL2 protein, human Rbl1 protein, mouse Rbl2 protein, mouse Retinoblastoma Protein Retinoblastoma-Like Protein p107 Retinoblastoma-Like Protein p130
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mulligan G J
Center for Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA.
Wong J
Jacks T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.1.206
Published
1998-01-00
Pages
206-20
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC121478
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.18.1.206 PMC Full Text View journal details
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