The lymphocyte
cell surface antigen CD38, which was originally described as a
differentiation marker, has emerged as an important multifunctional
protein. Its most intriguing and well characterized function is its ability to catalyze the synthesis of
cyclic ADP-ribose (
cADPR) from
NAD.
cADPR serves as an important second messenger in controlling the release of intracellular
calcium from
ryanodine-sensitive intracellular pools. By virtue of its ability to synthesize
cADPR as well as to act as an adhesion and signal transduction molecule, CD38 may play a role in such diverse physiological processes as cell growth, apoptosis, differentiation, and
inflammation. Equally interesting is the pattern of CD38 expression in hematopoietic cells. In the bone marrow, early precursor cells predominantly express
CD38 antigen, whereas mature circulating blood cells lack or express very low levels. The expression is also high on malignant hematopoietic cells and thus may be of prognostic relevance in certain
leukemias. Presently, there is little information available on the factors that regulate the expression of
CD38 antigen in hematopoietic cells. In this review, we summarize recent findings on the regulation of
CD38 antigen by
retinoids (
vitamin A and related compounds). At least in the myeloid cell lineage,
retinoids appear to be exquisitely potent and specific inducers of
CD38 antigen expression, and
retinoid-induced expression of CD38 is mediated via activation of the
retinoic acid-alpha (RAR alpha)
nuclear receptor.