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Molecular and Cellular Biology, February 1999, p. 1479-1485, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification of a Gene That Reverses the Immortal Phenotype of a Subset of Cells and Is a Member of a Novel Family of Transcription Factor-Like Genesdagger

M. J. Bertram,1,* N. G. Bérubé,1 X. Hang-Swanson,1 Q. Ran,1 J. K. Leung,1 S. Bryce,2 K. Spurgers,1 R. J. Bick,3 A. Baldini,4 Y. Ning,5 L. J. Clark,2 E. K. Parkinson,2 J. C. Barrett,6 J. R. Smith,1,7,8,9 and O. M. Pereira-Smith1,7,8,9

Roy M. and Phyllis Gough Huffington Center on Aging1 and Divisions of Molecular Virology9 and Molecular and Human Genetics4 and Departments of Cell Biology7 and Medicine,8 Baylor College of Medicine, and Department of Pathology, The University of Texas Medical School,3 Houston, Texas 77030; Beatson Cancer Institute, Glasgow, Scotland2; GeneCare, the Wilson Genetics Center, George Washington University Medical Center, Washington, D.C. 200375; and Laboratory of Molecular Carcinogenesis, National Institutes of Environmental Health Sciences, Research Triangle Park, North Carolina 277096

Received 24 June 1998/Returned for modification 9 October 1998/Accepted 30 October 1998

Based on the dominance of cellular senescence over immortality, immortal human cell lines have been assigned to four complementation groups for indefinite division. Human chromosomes carrying senescence genes have been identified, including chromosome 4. We report the cloning and identification of a gene, mortality factor 4 (MORF 4), which induces a senescent-like phenotype in immortal cell lines assigned to complementation group B with concomitant changes in two markers for senescence. MORF 4 is a member of a novel family of genes with transcription factor-like motifs. We present here the sequences of the seven family members, their chromosomal locations, and a partial characterization of the three members that are expressed. Elucidation of the mechanism of action of these genes should enhance our understanding of growth regulation and cellular aging.

* Corresponding author. Mailing address: Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3498. Phone: (713) 798-3599. Fax: (713) 798-4161. E-mail: mbertram{at}bcm.tmc.edu.

dagger This work is dedicated to the memory of Ruth Sager, a visionary scientist in the fields of senescence and tumor biology, among others.

Molecular and Cellular Biology, February 1999, p. 1479-1485, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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