title: New roles of carboxypeptidase E in endocrine and neural function and cancer.
abstract: Carboxypeptidase E (CPE) or carboxypeptidase H was first discovered in 1982 as an enkephalin-convertase that cleaved a C-terminal basic residue from enkephalin precursors to generate enkephalin. Since then, CPE has been shown to be a multifunctional protein that subserves many essential nonenzymatic roles in the endocrine and nervous systems. Here, we review the phylogeny, structure, and function of CPE in hormone and neuropeptide sorting and vesicle transport for secretion, alternative splicing of the CPE transcript, and single nucleotide polymorphisms in humans. With this and the analysis of mutant and knockout mice, the data collectively support important roles for CPE in the modulation of metabolic and glucose homeostasis, bone remodeling, obesity, fertility, neuroprotection, stress, sexual behavior, mood and emotional responses, learning, and memory. Recently, a splice variant form of CPE has been found to be an inducer of tumor growth and metastasis and a prognostic biomarker for metastasis in endocrine and nonendocrine tumors.
authors.affiliation: Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Niamh X
authors.initials: NX
authors.lastname: Cawley
authors.forename: William C
authors.initials: WC
authors.lastname: Wetsel
authors.forename: Saravana R K
authors.initials: SR
authors.lastname: Murthy
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Park
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
authors.forename: Y Peng
authors.initials: YP
authors.lastname: Loh
mesh_terms: D000818:Animals; D043423:Carboxypeptidase H / Q000502:physiology*; D002490:Central Nervous System / Q000201:enzymology*; D004703:Endocrine System / Q000201:enzymology*; D006801:Humans; D023421:Models, Animal; D009369:Neoplasms / Q000201:enzymology*
chemical_list: D043423:Carboxypeptidase H