HEAT-SHOCK INCREASES THE ASSOCIATION OF BINDING PROTEIN-1 WITH INITIATION-FACTOR 4E

The effects of heat shock on the regulation of the cap-binding initiat ion factor 4E (eIF4E) and its inhibitory binding protein, 4E-BP1, have been examined in Chinese hamster ovary cells and in cardiac myocytes. Heat shock increased the association between eIF4E and 4E-EP1, and th is was associated with a dephosphorylation of 4E-BP1. These effects di d not appear to be due wholly to decreased activity of the p70 S6 kina se pathway, which is implicated in the control of 4E-BP1, and they wer e not mediated by the stress-activated p38 microtubule-associated prot ein kinase pathway. Increased binding of 4E-BP1 to eIF4E correlated wi th a decrease in the amount of eIF4G which co-purified with the latter , This could account for the previously observed impairment of eIF4F f unction during heat shock, and, since heat shock protein mRNAs are bel ieved to be relatively cap-independent, could provide a mechanism for the selective up-regulation of the synthesis of heat shock proteins an d other stress proteins during heat shock.