Changes in proteasome expression and activity during differentiation of neuronal precursor NTera 2 clone D1 cells

The effect of differentiation of the human neuronal progenitor cell line NT era 2 clone D1 (NT2/D1) by retinoic acid on components of the proteasome sy stem was studied. The chymotrypsin-like and peptidylglutamyl peptide bond h ydrolyzing activities of the proteasome increased five weeks after retinoic acid, and following treatment with mitotic inhibitors returned to levels d etected in non-differentiated cells. A selective induction of the MHC class II region encoded LMP7 and LMP2 proteasome subunits occurred during differ entiation,, vr whereas there were no changes in the expression of the const itutive LMP2 counterpart (delta-subunit) or the constitutive C2 subunit. Im munofluoresence revealed marked LMP7 accumulation in fully differentiated c ells, with no changes in the labeling pattern of the constitutive proteasom e antigens. The expression of the alpha-subunit of the PA28 proteasome acti vator was down-regulated in fully differentiated neurons, but was not corre lated with changes in enzymatic activity. Changes in proteasome activity an d composition may contribute to the processes leading to differentiation of human neurons in vitro and to the properties of fully differentiated neuro ns. (C) 1999 Elsevier Science Ltd. All rights reserved.