14-3-3 epsilon has no homology to LIS1 and lies telomeric to it on chromosome 17p13.3 outside the Miller-Dieker syndrome chromosome region.
Previously, we isolated several cDNA clones of the LIS1 gene implicated in Miller-Dieker syndrome. Analysis of the 5' end of one of the clones (8-1), which was originally thought to represent the 5' end of LIS1, indicates a striking similarity to mouse 14-3-3 epsilon. We have isolated a full-length cDNA of human 14-3-3 epsilon, for which sequence analysis reveals a strong nucleotide conservation with mouse 14-3-3 epsilon in both translated and untranslated regions (UTRs). Additionally, the predicted peptides of human, sheep, rat, and mouse 14-3-3 epsilon are identical. Using a 205-bp fragment common to LIS1 (8-1) and 14-3-3 epsilon as probe on adult and fetal multiple-tissue Northern blots, a -2-kb transcript is detected, identical to the pattern observed with a full-length 14-3-3 epsilon cDNA probe. LIS1-specific transcripts of approximately 7.5 and approximately 5 kb are not detected by the 0.2-kb probe, indicating that the similarity between the 5' sequence of LIS1 (8-1) and the 3' UTR of 14-3-3 epsilon is not the result of shared homology between the two genes. Instead, clone 8-1 is a chimera of 14-3-3 epsilon and LIS1 partial cDNAs, and therefore its 5' sequence does not represent the LIS1 5' end. Interestingly, we have mapped the 14-3-3 epsilon gene to the same chromosomal sub-band as LIS1 (17p13.3). However, 14-3-3 epsilon lies telomeric to LIS1 and outside the Miller-Dieker syndrome chromosome region but in a region frequently deleted in several types of cancer, and is a reasonable candidate tumor suppressor gene.
Chong
S S
SS
National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Tanigami
A
A
Roschke
A V
AV
Ledbetter
D H
DH
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D048948:14-3-3 Proteins; D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D051381:Rats; D017421:Sequence Analysis; D012756:Sheep; D013577:Syndrome; D016615:Telomere / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D011506:Proteins; D014446:Tyrosine 3-Monooxygenase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; C513190:Pafah1b1 protein, mouse