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 genes.
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.
Bertram
M J
MJ
Roy M. and Phyllis Gough Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA. mbertram@bcm.tmc.edu
Bérubé
N G
NG
Hang-Swanson
X
X
Ran
Q
Q
Leung
J K
JK
Bryce
S
S
Spurgers
K
K
Bick
R J
RJ
Baldini
A
A
Ning
Y
Y
Clark
L J
LJ
Parkinson
E K
EK
Barrett
J C
JC
Smith
J R
JR
Pereira-Smith
O M
OM
D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics*; D015870:Gene Expression; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D015345:Oligonucleotide Probes / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
C109882:MORF4 protein, human; C491668:MORF4L1P1 protein, human; C491669:MORF4L2 protein, human; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014157:Transcription Factors