LIMITED DEGRADATION OF RETINOID-X RECEPTOR BY CALPAIN

Recently, we have found two major physiological forms of retinoid X re ceptor alpha (RXR alpha): the mature 54 kDa RXR alpha and the truncate d 44 kDa RXR alpha lacking a portion of N-terminal A/B domain in human and rodent livers. In this communication, we show that m-calpain was active to digest 54 kDa RXR alpha in the human hepatoma-derived cell l ine, HuH7, nuclei to 44 kDa fragment through 47 kDa intermediate in vi tro. Although both proteolytic fragments were revealed by anti-RXR alp ha antibody against its E-domain, neither fragment reacted with anti-R XR alpha antibody specific for A/B domain. The profile of the calpain- induced proteolytic fragmentation of RXR alpha was almost identical to that of endogenous RXR alpha in nonmalignant human and normal mouse l iver nuclei. This is the first demonstration that RXR alpha is a subst rate for m-calpain, strongly suggesting that the enzyme might also be involved in post-translational modification of the receptor in hepatoc ytes. (C) 1996 Academic Press, Inc.