Regulation of lactate dehydrogenase gene expression by cAMP-dependent protein kinase subunits

The studies described in this report suggest a rather complex, albeit incomplete, sequence of molecular events that we believe form part of the cascade of reactions through which a series of hormones, via cAMP, regulates the expression of specific gene products. The majority of our own studies relate to cAMP-mediated induction of LDH. Some, if not all, of the molecular steps discussed in this paper may ultimately be recognized as part of a universal mechanism by which cAMP controls gene expression in higher eukaryotes. The idea of a functional role for cAMP-dependent protein kinase subunits in cAMP-mediated gene control has already had experimental support, but our identification of the regulatory subunit RII as a topoisomerase now more firmly points to a complex function for the kinase in regulating gene function at the DNA level. We look forward to the elucidation of the function of those nuclear proteins that serve as substrate for the catalytic subunit of cAMP-dependent protein kinase. Further studies related to the molecular interaction of RII with chromosomal DNA should be a fruitful area for future research.