Various factors are involved in the heat shock-induced inhibition of
protein synthesis. Changes upon heat shock in phosphorylation, leading to inactivation, of
eukaryotic initiation factors (eIFs)
eIF2 and
eIF4E have been shown for several cell types. However, in mammalian cells these changes occur at temperatures of 43 degrees C or higher while
protein synthesis is already affected at milder heat shock temperatures. In searching for the cause for the inhibition of
protein synthesis, the regulation of
eIF2 and
eIF4E by additional factors was analyzed. In this respect, the activity of
eIF2B was measured during and after heat shock. A very clear correlation was found between the activity of this
guanine exchange factor and the levels of
protein synthesis, also at mild heat shock conditions. Changes in the phosphorylation of
eIF4E and of the eIF4E-binding
protein PHAS-I were also analyzed. Surprisingly, in H35 cells as well as in some other cell lines, PHAS-I phosphorylation was increased by heat shock, whereas in others it was decreased. Therefore, decreasing the
eIF4E availability under stressful conditions does not seem to be a general mechanism to inhibit
protein synthesis by heat shock. Regulation of
eIF2B activity appears to be the main mechanism to control translation initiation after heat shock at mild temperatures.