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Intracellular Peptides in Cell Biology and Pharmacology

Special Laboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signaling—CeTICS, Butantan Institute, São Paulo SP 05503-900, Brazil
Proteimax Biotecnologia LTDA, São Paulo SP 05581-001, Brazil
Remer Consultores Ltda., São Paulo SP 01411-001, Brazil
Department of Biochemistry, Chemistry Institute, University of São Paulo 1111, São Paulo 05508-000, Brazil
Department of Cell and Developmental Biology, University of São Paulo (USP), São Paulo 05508-000, Brazil
Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, Brazil
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(4), 150;
Received: 28 February 2019 / Revised: 2 April 2019 / Accepted: 12 April 2019 / Published: 16 April 2019
(This article belongs to the Special Issue The Broader Cellular Impact of Proteasome-CSN-eIf3 (PCI) Complexes)
Intracellular peptides are produced by proteasomes following degradation of nuclear, cytosolic, and mitochondrial proteins, and can be further processed by additional peptidases generating a larger pool of peptides within cells. Thousands of intracellular peptides have been sequenced in plants, yeast, zebrafish, rodents, and in human cells and tissues. Relative levels of intracellular peptides undergo changes in human diseases and also when cells are stimulated, corroborating their biological function. However, only a few intracellular peptides have been pharmacologically characterized and their biological significance and mechanism of action remains elusive. Here, some historical and general aspects on intracellular peptides’ biology and pharmacology are presented. Hemopressin and Pep19 are examples of intracellular peptides pharmacologically characterized as inverse agonists to cannabinoid type 1 G-protein coupled receptors (CB1R), and hemopressin fragment NFKF is shown herein to attenuate the symptoms of pilocarpine-induced epileptic seizures. Intracellular peptides EL28 (derived from proteasome 26S protease regulatory subunit 4; Rpt2), PepH (derived from Histone H2B type 1-H), and Pep5 (derived from G1/S-specific cyclin D2) are examples of peptides that function intracellularly. Intracellular peptides are suggested as biological functional molecules, and are also promising prototypes for new drug development. View Full-Text
Keywords: intracellular peptides; proteasome; epilepsy; endocannabinoid; cancer; drug discovery; obesity; insulin resistance intracellular peptides; proteasome; epilepsy; endocannabinoid; cancer; drug discovery; obesity; insulin resistance
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de Araujo, C.B.; Heimann, A.S.; Remer, R.A.; Russo, L.C.; Colquhoun, A.; Forti, F.L.; Ferro, E.S. Intracellular Peptides in Cell Biology and Pharmacology. Biomolecules 2019, 9, 150.

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