Effect of all-trans retinoic acid on post translational regulation and subcellular distribution of the oncosuppressor GRIM 19

GRIM-19 is an oncosuppressor which antagonizes the oncogene Stat 3. GRIM19 is partitioned between the nucleus and mitochondria where it appears as a subunit of respiratory complex I. Our group has studied the impact of the chemiotherapic agent all-trans- retinoic acid (ATRA) on the subcellular distribution of GRIM-19. The results show that ATRA treatment of keratinocytes results in increased level of GRIM-19 and other subunits of complex I, in particular of their carbonylated forms, associated with inhibition of its enzymatic activity. In keratinocytes ATRA-promoted phosphatase activity appears to control the proteostasis and activity of complex I. Furthermore, the oncogene STAT-3, besides being localized in the nucleus, has also been found in mitochondria where it interacts with GRIM 19. Thus, perturbation of the interplay of GRIM 19 with factors, associated with complex I, can be involved in the ATRA suppression of keratinocyte growth.