LEM3 (ligand-effect modulator 3) family / CDC50 family
Members of this family have been predicted to contain transmembrane helices. The family member LEM3 is a ligand-effect modulator, mutation of which increases glucocorticoid receptor activity in response to dexamethasone and also confers increased activity on other intracellular receptors including the progesterone, oestrogen and mineralocorticoid receptors. LEM3 is thought to affect a downstream step in the glucocorticoid receptor pathway. Factors that modulate ligand responsiveness are likely to contribute to the context-specific actions of the glucocorticoid receptor in mammalian cells. The products of genes YNR048w, YNL323w, and YCR094w (CDC50) show redundancy of function and are involved in regulation of transcription via CDC39. CDC39 (also known as NOT1) is normally a negative regulator of transcription either by affecting the general RNA polymerase II machinery or by altering chromatin structure. One function of CDC39 is to block activation of the mating response pathway in the absence of pheromone, and mutation causes arrest in G1 by activation of the pathway. It may be that the cold-sensitive arrest in G1 noticed in CDC50 mutants may be due to inactivation of CDC39. The effects of LEM3 on glucocorticoid receptor activity may also be due to effects on transcription via CDC39.