A novel PHD-finger motif protein, p47ING3, modulates p53-mediated transcription, cell cycle control, and apoptosis.
A candidate tumor suppressor gene, p33ING1, was previously identified by using the genetic suppressor element methodology. p33ING1 cooperates with p53 and plays a significant role in p53-mediated cellular processes. Recently, we have identified p33ING2, which shows a sequence homology similar to p33ING1 and modulates p53 function. In the present study, we identified and characterized another 'ING family' gene. The estimated molecular weight of the encoded protein is 46.8 kDa, thus, we named it p47ING3. The p47ING3 gene is located at chromosome 7q31.3 and consists of 12 exons that encode 418 amino acids. A computational domain search revealed a C-terminal PHD-finger motif. Such motifs are common in proteins involved in chromatin remodeling. p47ING3 is highly expressed in some normal human tissues or organs, including the spleen, testis, skeletal muscle, and heart. p47ING3 expression levels varied among cancer cell lines. p47ING3 overexpression resulted in a decreased population of cells in S phase, a diminished colony-forming efficiency, and induced apoptosis in RKO cells, but not in RKO-E6 cells with inactivated p53. p47ING3 activates p53-transactivated promoters, including promoters of p21/waf1 and bax. Thus, we have isolated a novel ING family gene, p47ING3, which modulates p53-mediated transcription, cell cycle control, and apoptosis.
Nagashima
Makoto
M
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA.
Shiseki
Masayuki
M
Pedeux
Remy M
RM
Okamura
Shu
S
Kitahama-Shiseki
Mariko
M
Miura
Koh
K
Yokota
Jun
J
Harris
Curtis C
CC
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7; D005091:Exons; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear; D012016:Reference Values; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D016335:Zinc Fingers
D018398:Homeodomain Proteins; C444654:ING2 protein, human; C459806:ING3 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins