ALPHA-B-CRYSTALLIN EXPRESSION IN MOUSE NIH 3T3 FIBROBLASTS - GLUCOCORTICOID RESPONSIVENESS AND INVOLVEMENT IN THERMAL PROTECTION

AlphaB-crystallin, a major soluble protein of vertebrate eye lenses, is a small heat shock protein which transiently accumulates in response to heat shock and other kinds of stress in mouse NIH 3T3 fibroblasts. EctoPic expression of an alphaB-crystallin cDNA clone renders NIH 3T3 cells thermoresistant. AlphaB-crystallin accumulates in response to the synthetic glucocorticoid hormone dexamethasone. Dexamethasone-treated NIH 3T3 cells become thermoresistant to the same extent as they accumulate alphaB-crystallin. A cell done in which alphaB-crystallin is superinduced upon heat shock acquires augmented thermotolerance. Expression of the ras oncogene causes a rapid but transient accumulation of alphaB-crystallin within 1 day. Later, sustained ras oncogene expression suppresses the dexamethasone-mediated alphaB-crystallin accumulation. Thus, oncogenic transformation triggered by the ras oncogene interferes with hormone-mediated accumulation of alphaB-crystallin and concomitant acquisition of thermoresistance. Other known heat shock proteins do not accumulate in response to ectopic alphaB-crystallin expression or to dexamethasone treatment. These results indicate that alphaB-crystallin can protect NIH 3T3 fibroblasts from thermal shock.