THE TRANSGLUTAMINASE-1 ENZYME IS VARIABLY ACYLATED BY MYRISTATE AND PALMITATE DURING DIFFERENTIATION IN EPIDERMAL-KERATINOCYTES

The transglutaminase 1 (TGase 1) enzyme is involved in the formation o f a cornified cell envelope in terminally differentiating epidermal ke ratinocytes. The enzyme is present in proliferating cells but is more abundantly expressed in differentiating cells and exists in several in tact or proteolytically processed cytosolic or membrane-anchored forms , We show here that the equilibrium partitioning of TGase 1 between th e cytosol and membranes is controlled by variable modification by myri state and palmitate, During synthesis, it is constitutively N-myristoy lated. Later, it is modified by an average of two S-myristoyl adducts in proliferating cells or one S-palmitoyl adduct in differentiating ce lls. The three myristoyl adducts of the former provide more robust anc horage to membranes than the one myristoyl and one palmitoyl adduct of the latter, The half-lives of the S-myristoyl and especially the S-pa lmitoyl adducts are less than that of the TGase 1 protein, suggesting a mechanism for cycling off membranes. In in vitro overlay assays, the S-acylated 10-kDa anchorage fragment facilitates binding of TGase 1 f orms, supporting a mechanism of cycling back onto membranes in vivo. W e conclude that differential acylation increases the repertoire of fun ctional TGase 1 forms, depending on the differentiation state of epide rmal keratinocytes.