Modifications of ornithine decarboxylase induced by phosphatases.

Abstract

The sensitivity with which a tissue regulates polyamine biosynthesis during normal growth, development and hormone response has long been appreciated, but not well understood. In particular, the activity of the initial enzyme in this pathway, ornithine decarboxylase (ODC), appears to be subject to many cellular regulatory signals. Through recent advances in cDNA probes for ODC mRNA, and the use of radioactively labeled DFMO to tag ODC, along with the isolation and use of monospecific antibodies, great progress has been made in our understanding of the control of ODC synthesis at the levels of transcription and translation. However, this enzyme protein is also noted for its unusual instability (T1/2 can be less than 20 min) in mammalian tissues, and therefore the factors influencing this instability must also be considered if we are to gain complete understanding of the observed rapid modulation of cellular ODC activity. Unfortunately very little is known about how a cell may rapidly target and specifically degrade such a protein. This process must be of great significance, as this extreme enzyme instability is not common among cellular proteins, yet it is a feature shared by many proto-oncogene products.