title: Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology.
abstract: The membrane proteins CD38 and CD157 belong to an evolutionarily conserved family of enzymes that play crucial roles in human physiology. Expressed in distinct patterns in most tissues, CD38 (and CD157) cleaves NAD(+) and NADP(+), generating cyclic ADP ribose (cADPR), NAADP, and ADPR. These reaction products are essential for the regulation of intracellular Ca(2+), the most ancient and universal cell signaling system. The entire family of enzymes controls complex processes, including egg fertilization, cell activation and proliferation, muscle contraction, hormone secretion, and immune responses. Over the course of evolution, the molecules have developed the ability to interact laterally and frontally with other surface proteins and have acquired receptor-like features. As detailed in this review, the loss of CD38 function is associated with impaired immune responses, metabolic disturbances, and behavioral modifications in mice. CD38 is a powerful disease marker for human leukemias and myelomas, is directly involved in the pathogenesis and outcome of human immunodeficiency virus infection and chronic lymphocytic leukemia, and controls insulin release and the development of diabetes. Here, the data concerning diseases are examined in view of potential clinical applications in diagnosis, prognosis, and therapy. The concluding remarks try to frame all of the currently available information within a unified working model that takes into account both the enzymatic and receptorial functions of the molecules.
authors.affiliation: Laboratory of Immunogenetics, Department of Genetics, Biology, and Biochemistry and Centro di Ricerca in Medicina Sperimentale, University of Torino Medical School, Torino, Italy. fabio.malavasi@unito.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Ada
authors.initials: A
authors.lastname: Funaro
authors.forename: Enza
authors.initials: E
authors.lastname: Ferrero
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Horenstein
authors.forename: Erika
authors.initials: E
authors.lastname: Ortolan
authors.forename: Tiziana
authors.initials: T
authors.lastname: Vaisitti
authors.forename: Semra
authors.initials: S
authors.lastname: Aydin
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D058851:GPI-Linked Proteins; D006801:Humans; D007113:Immunity, Innate; D018796:Immunoconjugates / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods; D008024:Ligands; D023421:Models, Animal; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D015398:Signal Transduction / Q000276:immunology; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D018796:Immunoconjugates; D008024:Ligands; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2; D051997:ADP-ribosyl Cyclase 1