J Biol Chem, Vol. 274, Issue 23, 16487-16493, June 4, 1999

Cloning and Characterization of a Human Genotoxic and Endoplasmic Reticulum Stress-inducible cDNA That Encodes Translation Initiation Factor 1(eIF1^A121/SUI1)

M. Saeed Sheikh, Ester Fernandez-Salas^¶, Myounghee Yu, Arif Hussain, Jonathan D. Dinman^**, Stuart W. Peltz^**, Ying Huang, and Albert J. Fornace Jr.

From the  Division of Basic Sciences and ^¶ Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda MD 20892,  Greenbaum Cancer Center, University of Maryland, Baltimore MD 21201, ^** Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey (UMDNJ), Robert Wood Johnson Medical School and The Graduate Programs in Molecular Bioscience Rutgers/UMDNJ, Piscataway, New Jersey 08854, and  Laboratory of Biological Chemistry, NIA, National Institutes of Health, Baltimore, Maryland 21224

We report the cloning and characterization of a DNA damage-inducible (DDI) transcript DDI A121. The full-length human DDI A121 cDNA contains an open reading frame of 113 amino acids, corresponding to a protein of 12.7 kDa. The deduced amino acid sequence of A121 shows high homology to the yeast translation initiation factor (eIF) sui1 and also exhibits perfect identity to the partial sequence of recently purified human eIF1. Expression of human A121 corrected the mutant sui1 phenotype in yeast, demonstrating that human A121 encodes a bona fide translation initiation factor that is equivalent to yeast sui1p. The mammalian A121/SUI1 gene exhibits two transcripts (1.35 kilobases and 0.65 kilobases) containing a common coding region but differing in their 3'-untranslated region. The long and short A121/SUI1 mRNAs are differentially regulated by genotoxic and endoplasmic reticulum stress. The genotoxic stress induction of A121/SUI1 mRNA is conserved in both humans and rodents and occurs in a p53-independent manner. Our identification of a stress-inducible cDNA that encodes eIF1 suggests that modulation of translation initiation appears to occur during cellular stress and may represent an important adaptive response to genotoxic as well as endoplasmic reticulum stress.