IDENTIFICATION OF SERUM-INDUCIBLE GENES - DIFFERENT PATTERNS OF GENE-REGULATION DURING G(0)-]S AND G(1)-]S PROGRESSION

We have identified, by differential cDNA library screening, 15 serum i nducible genes in the human diploid fibroblast cell line WI-38. The ge nes fall into two classes that are distinguished by their dependence o n protein synthesis for the induction by serum, i.e., primary and seco ndary genes. While 11 of these genes encode known proteins, 4 other ge nes have not been described to date. The former genes encode proteins of diverse functions, including the monocyte-derived neutrophil chemot actic factor (MONAP), calmodulin, tropomyosin, tenascin, collagenase, plasminogen activator inhibitor-2a, the 'sperm-specific' cleavage sign al-1 protein, metallothionein IIa and the mitochondrial chaperonin hsp -60. Interestingly, one of the unknown genes contains a large open rea ding frame for a polypeptide that is highly homologous to a previously unidentified long open reading frame in the opposite strand of the ge ne coding for the transcription factor HTF-4. We also studied the regu lation of these serum-induced genes during cell cycle progression in n ormally cycling WI-38 and HL-60 cells separated by counterflow elutria tion as well as in serum-stimulated HL-60 cells. Our results clearly s how that, in contrast to the prevailing opinion, the expression of mos t genes induced after mitogen stimulation is not subject to a signific ant regulation in normally proliferating cells. This supports the hypo thesis that the progression into S from either G(0) or G(1) are distin ct processes with specific patterns of gene expression.