Regulation of nuclear Prointerleukin-16 and p27(Kip1) in primary human T lymphocytes.
Prointerleukin-16 (Pro-IL-16) is an abundant, PDZ domain-containing protein expressed in the nucleus and cytoplasm of resting human T lymphocytes. We have previously shown that ectopic expression of Pro-IL-16 in Pro-IL-16-negative human Jurkat cells represses transcription of the F-box protein, Skp2, resulting in accumulation of the cyclin-dependent kinase inhibitor, p27(Kip1), and G0/G1 cell cycle arrest. The current studies demonstrate the kinetics of Pro-IL-16 and p27(Kip1) expression in activated normal human T lymphocytes. We correlate nuclear Pro-IL-16 loss with decreased p27(Kip1) expression, increased cell cycle progression, and proliferation. Conversely, we show that constitutive expression of Pro-IL-16 by retroviral infection of activated human T lymphocytes induces G0/G1 cell cycle arrest, inhibits proliferation, and is associated with increased levels of p27(Kip1). These findings implicate nuclear Pro-IL-16 as a cell cycle regulatory protein for human T lymphocytes.
Wilson
Kevin C
KC
The Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. kwilson@lung.bumc.bu.edu
Cattel
Dennis J
DJ
Wan
Zhi
Z
Rahangdale
Shilpa
S
Ren
Fucheng
F
Kornfeld
Hardy
H
Sullivan
Beth A
BA
Cruikshank
William W
WW
Center
David M
DM
D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D019410:Interleukin-16 / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000276:immunology; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
C436291:CDKN1B protein, human; D018797:Cell Cycle Proteins; D019410:Interleukin-16; D047908:Intracellular Signaling Peptides and Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C105950:interleukin 16 precursor; D050760:Cyclin-Dependent Kinase Inhibitor p27