TRANSIENT ACCUMULATION, PHOSPHORYLATION AND CHANGES IN THE OLIGOMERIZATION OF HSP27 DURING RETINOIC ACID-INDUCED DIFFERENTIATION OF HL-60 CELLS - POSSIBLE ROLE IN THE CONTROL OF CELLULAR GROWTH AND DIFFERENTIATION

Expression of the mammalian small stress protein Hsp27 has been increa singly linked to cell growth regulation and differentiation. Hsp27 is a phosphoprotein which forms oligomers with native sizes ranging betwe en 100 and 800 kDa. We have examined the fate of Hsp27 transiently exp ressed during the retinoic acid (tRA)-induced granulocytic differentia tion of human leukemic HL-60 cells. We show that tRA, in addition to i ts effects on Hsp27 accumulation and phosphorylation, transiently incr eased the oligomerization state of this protein. While Hsp27 phosphory lation by tRA is an early phenomenon that takes place before cellular growth is altered, the redistribution of Hsp27 oligomers occurred late r and concomitantly with the maximal accumulation of this protein. Hen ce, complex regulations of Hsp27 are induced by tRA which suggest that this protein plays a role in the pathway through which retinoids exer t their effects. To approach Hsp27 function during HL-60 cell differen tiation, experiments aimed at reducing the cellular content of this pr otein were performed by transiently inhibiting Hsp27 mRNA translation by a specific anti-sense oligonucleotide. This process, which decrease d the basal level of Hsp27 by about 40%, did not interfere with the gr owth of undifferentiated HL-60 cells. In contrast, a decreased level o f Hsp27 diminished the differentiation-mediated down-regulation of cel l growth and altered some morphological changes induced by this retino id. These results suggest that Hsp27 is a mediator of granulocytic dif ferentiation.