Luman Potentially Regulates Metabolism Through Modulation of the Hypothalamic-Pituitary-Adrenal Axis

Luman is an endoplasmic reticulum associated transmembrane protein which when activated, alleviates endoplasmic reticulum stress. Recently, Luman has been found to play a key role in glucocorticoid signaling which modulates the whole-body stress response; this interaction is hypothesized to be due to an interaction with the glucocorticoid receptor. Luman contains a motif which is a hallmark of general nuclear receptor cofactors, suggesting that Luman may be able to interact not just with the glucocorticoid receptor but with all nuclear steroid hormone receptors. Luman may also affect neuronal regulation of steroid hormone signaling by protecting against endoplasmic reticulum stress. Here we demonstrate that Luman directly interacts with the glucocorticoid receptor through this canonical nuclear receptor binding domain and that Luman may act as a general cofactor of other nuclear receptors. These data provide more evidence that Luman may impact whole body steroid hormone signaling through modulation of nuclear receptors.