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Genetic and Functional Analyses Exclude Mortality Factor 4 (MORF4) as a Keratinocyte Senescence Gene¹

Beatson Institute for Cancer Research, CRC Beatson Laboratories, Bearsden, Glasgow, G61 1BD United Kingdom [S. D. B., N. R. F., S. A. F., L. J. C., E. K. P.]; Roy M. and Phyllis Gough Huffington Center on Ageing, Baylor College of Medicine, Houston, Texas 77030 [M. J. B., O. M. P-S.]; and Departments of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex, UB8 3PH United Kingdom [A. P. C., R. F. N.]

Approximately 50% of immortal human keratinocyte lines show loss of heterozygosity of chromosome region 4q33-q34, and the reintroduction of chromosome 4 into one such line, BICR 6, causes proliferation arrest and features of replicative senescence. Recently, a candidate gene, mortality factor 4 (MORF4), was identified in this region and sequenced in 21 immortal keratinocyte lines. There were no mutations or deletions, and two of the seven lines that showed loss of heterozygosity at 4q33-q34 were heterozygous for MORF4 itself. Furthermore, the transfer of a chromosomal segment containing the entire MORF4 gene did not mimic the senescence effect of chromosome 4 in BICR 6. These results suggest that the inactivation of MORF4 is not required for human keratinocyte immortality.