Upregulation of chicken p15INK4b at senescence and in the developing brain.
In mammalian cells, products of the INK4a-ARF locus play major roles in senescence and tumour suppression in different contexts, whereas the adjacent INK4b gene is more generally associated with transforming growth factor beta (TGF-beta)-mediated growth arrest. As the chicken genome does not encode an equivalent of INK4a, we asked whether INK4b and/or ARF contribute to replicative senescence in chicken cells. In chicken embryo fibroblasts (CEFs), INK4b levels increase substantially at senescence and the gene is transcriptionally silenced in two spontaneously immortalised chicken cell lines. By contrast, ARF levels are unaffected by prolonged culture or immortalisation. These expression patterns resemble the behaviour of INK4a and ARF in human fibroblasts. However, short-hairpin RNA (shRNA)-mediated knockdown of chicken INK4b or ARF provides only modest lifespan extension, suggesting that other factors contribute to senescence in CEFs. As well as underscoring the importance of the INK4b-ARF-INK4a locus in senescence, these findings imply that the encoded products have assumed different roles in different evolutionary niches. Although ARF RNA is not detectable in early chicken embryos, the INK4b transcript is expressed in the roof-plate of the developing hind-brain, consistent with a role in limiting cell proliferation.
Kim
Soo-Hyun
SH
Molecular Oncology, Cancer Research UK London Research Institute, Lincoln's Inn Fields, London, WC2A 3PX, UK.
Rowe
Janice
J
Fujii
Hideta
H
Jones
Rebecca
R
Schmierer
Bernhard
B
Kong
Byung-Whi
BW
Kuchler
Karl
K
Foster
Douglas
D
Ish-Horowicz
David
D
Peters
Gordon
G
D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D002642:Chick Embryo / Q000254:growth & development; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D034741:RNA, Small Interfering; D025803:Tumor Suppressor Protein p14ARF