Cited by 866Calcium signaling and nucleotide metabolismBiochemical and Molecular ResearchSirtuins and Resveratrol in Medicine

Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology

Malavasi, Fabio, Deaglio, Silvia, Funaro, Ada, Ferrero, Enza, Horenstein, Alberto L., Ortolan, Erika, Vaisitti, Tiziana, Aydin, Semra·2008·Physiological Reviews

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.

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Crossref · 10.1152/physrev.00035.2007

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Authors
Malavasi, F., Deaglio, S., Funaro, A., Ferrero, E., Horenstein, A. L., Ortolan, E., Vaisitti, T., & Aydin, S.
Affiliations
University of Turin (IT)
Venue
Physiological Reviews
Published
2008-07
Volume
88
Issue
3
Pages
841-886
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
OpenAlex
W2123895023
Cited by
862
References
374
Citations by year
2026: 40 · 2025: 35 · 2024: 48 · 2023: 60 · 2022: 61 · 2021: 75 · 2020: 81 · 2019: 53 · 2018: 51 · 2017: 52 · 2016: 38 · 2015: 44 · 2014: 40 · 2013: 34 · 2012: 44
FWCI
3.25
Type
journal article
Language
en
Open access
closed
Locations
  • Physiological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
CD38, CD157, ADP-ribosyl cyclase, cyclic ADP-ribose, NAADP, NAD+ metabolism, intracellular calcium signaling, enzyme evolution, immune response, leukemia, multiple myeloma, HIV infection, chronic lymphocytic leukemia, insulin secretion, diabetes mellitus, disease markers
MeSH terms
Animals, Antibodies, Monoclonal, Disease Models, Animal, Humans, Immunity, Innate, Immunotherapy, Ligands, Models, Molecular, Phylogeny, Protein Conformation, Tissue Distribution, Signal Transduction, Antigens, CD, Immunoconjugates, Evolution, Molecular, Models, Animal, ADP-ribosyl Cyclase, ADP-ribosyl Cyclase 1, GPI-Linked Proteins

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