Nuclear pro-IL-16 regulation of T cell proliferation: p27(KIP1)-dependent G0/G1 arrest mediated by inhibition of Skp2 transcription.
The precursor for IL-16 (pro-IL-16) is a nuclear and cytoplasmic PDZ domain-containing protein. In this study we have found that pro-IL-16 is absent or mutated in four T lymphoblastic leukemia cell lines examined. Ectopic expression of pro-IL-16 in pro-IL-16-negative Jurkat cells blocks cell cycle progression from G(0)/G(1) to S phase associated with elevated levels of the cyclin-dependent kinase inhibitor p27(KIP1). Pro-IL-16 decreases p27(KIP1) degradation by reducing transcription and subsequent expression of Skp2, a key component of the SCF(Skp2) ubiquitin E3 ligase complex. Taken together, these findings identify pro-IL-16 as a novel regulator of Skp2 expression and p27(KIP1) levels and implicate a role for pro-IL-16 in T cell proliferation.
Center
David M
DM
The Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA.
Cruikshank
William W
WW
Zhang
Yujun
Y
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D016193:G1 Phase / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019410:Interleukin-16 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015458:Leukemia, T-Cell / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D043743:Ubiquitin-Protein Ligase Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism
D018797:Cell Cycle Proteins; D019410:Interleukin-16; D009687:Nuclear Proteins; D011498:Protein Precursors; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; C105950:interleukin 16 precursor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D043743:Ubiquitin-Protein Ligase Complexes