HLS5, a novel RBCC (ring finger, B box, coiled-coil) family member isolated from a hemopoietic lineage switch, is a candidate tumor suppressor.
Hemopoietic cells, apparently committed to one lineage, can be reprogrammed to display the phenotype of another lineage. The J2E erythroleukemic cell line has on rare occasions developed the features of monocytic cells. Subtractive hybridization was used in an attempt to identify genes that were up-regulated during this erythroid to myeloid transition. We report here on the isolation of hemopoietic lineage switch 5 (Hls5), a gene expressed by the monocytoid variant cells, but not the parental J2E cells. Hls5 is a novel member of the RBCC (Ring finger, B box, coiled-coil) family of genes, which includes Pml, Herf1, Tif-1alpha, and Rfp. Hls5 was expressed in a wide range of adult tissues; however, at different stages during embryogenesis, Hls5 was detected in the branchial arches, spinal cord, dorsal root ganglia, limb buds, and brain. The protein was present in cytoplasmic granules and punctate nuclear bodies. Isolation of the human cDNA and genomic DNA revealed that the gene was located on chromosome 8p21, a region implicated in numerous leukemias and solid tumors. Enforced expression of Hls5 in HeLa cells inhibited cell growth, clonogenicity, and tumorigenicity. It is conceivable that HLS5 is one of the tumor suppressor genes thought to reside at the 8p21 locus.
Lalonde
Jean-Philippe
JP
Laboratory for Cancer Medicine, Western Australian Institute for Medical Research, Royal Perth Hospital and the Center for Medical Research, The University of Western Australia, Perth, Western Australia 6000, Australia.
Lim
Raelene
R
Ingley
Evan
E
Tilbrook
Peta A
PA
Thompson
Martin J
MJ
McCulloch
Ross
R
Beaumont
Jennifer G
JG
Wicking
Carol
C
Eyre
Helen J
HJ
Sutherland
Grant R
GR
Howe
Kathy
K
Solomon
Ellen
E
Williams
James H
JH
Klinken
S Peter
SP
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D001934:Branchial Region / Q000737:chemistry / Q000196:embryology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D002898:Chromosomes, Human, Pair 8; D003594:Cytoplasmic Granules / Q000737:chemistry; D004247:DNA / Q000032:analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D005314:Embryonic and Fetal Development; D005121:Extremities / Q000196:embryology; D005727:Ganglia, Spinal / Q000737:chemistry / Q000196:embryology; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D013116:Spinal Cord / Q000737:chemistry / Q000196:embryology; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; C476418:TRIM35 protein, human; D004247:DNA