Proliferating cell nuclear antigen as the cell cycle sensor for an HLA-derived peptide blocking T cell proliferation Journal Article
| Authors: | Ling, X.; Kamangar, S.; Boytim, M. L.; Kelman, Z.; Huie, P.; Lyu, S. C.; Sibley, R. K.; Hurwitz, J.; Clayberger, C.; Krensky, A. M. |
| Article Title: | Proliferating cell nuclear antigen as the cell cycle sensor for an HLA-derived peptide blocking T cell proliferation |
| Abstract: | Synthetic peptides corresponding to structural regions of HLA molecules are novel immunosuppressive agents. A peptide corresponding to residues 65-79 of the α-chain of HLA-DQA03011 (DQ65-79) blocks cell cycle progression from early G1 to the G1 restriction point, which inhibits cyclin-dependent kinase-2 activity and phosphorylation of the retinoblastoma protein. A yeast two-hybrid screen identified proliferating cell nuclear Ag (PCNA) as a cellular ligand for this peptide, whose interaction with PCNA was further confirmed by in vitro biochemistry. Electron microscopy demonstrates that the DQ65-79 peptide enters the cell and colocalizes with PCNA in the T cell nucleus in vivo. Binding of the DQ65-79 peptide to PCNA did not block polymerase δ (pol δ)-dependent DNA replication in vitro. These findings support a key role for PCNA as a sensor of cell cycle progression and reveal an unanticipated function for conserved regions of HLA molecules. |
| Keywords: | protein phosphorylation; human cell; dna replication; lymphocyte proliferation; t lymphocyte; cell cycle; protein binding; retinoblastoma; phosphorylation; lymphocyte activation; peptide fragments; ligands; cycline; retinoblastoma protein; immunosuppressive agents; cell cycle g1 phase; hla antigen; two-hybrid system techniques; proliferating cell nuclear antigen; mitosis inhibition; cell nucleus antigen; dna polymerase iii; humans; human; priority journal; article; hla-dq antigens |
| Journal Title: | Journal of Immunology |
| Volume: | 164 |
| Issue: | 12 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2000-06-15 |
| Start Page: | 6188 |
| End Page: | 6192 |
| Language: | English |
| PUBMED: | 10843669 |
| PROVIDER: | scopus |
| DOI: | 10.4049/jimmunol.164.12.6188 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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