Proteases and posttranslational processing of prohormones: a review

Lazure, Claude; Seidah, Nabil G.; Pélaprat, Didier; Chrétien, Michel

doi:10.1139/o83-066

Cited by 138 publications

(64 citation statements)

References 54 publications

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“…The latter is then further cleaved at Leul-Ala2, Ala2-Gly3, and Leu7-Arg8 to yield ANF- (1-33), -(2-33), -(3-33), and -(8-33), respectively. None of the cleavages involve maturation at pairs of basic residues, as would be expected from studies of precursorproduct maturation (21). Also puzzling is the absence of appreciable cleavage after the pair of basic residues Arg8-Argg (Fig.…”

Section: Discussionmentioning

confidence: 82%

Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

Seidah¹,

Lazure²,

Chrétien³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

184

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A substance called atrial natriuretic factor (ANF), localized in secretory granules of atrial cardiocytes, was isolated as four homologous natriuretic peptides from homogenates of rat atria. The complete sequence of the longest form showed that it is composed of 33 amino acids. The three other shorter forms (2-33, 3-33, and 8-33) represent aminoterminally truncated versions of the 33 amino acid parent molecule as shown by analysis of sequence, amino acid composition, or both. The proposed primary structure agrees entirely with the amino acid composition and reveals no significant sequence homology with any known protein or segment of protein. The short form ANF-(8-33) was synthesized by a multifragment condensation approach and the synthetic product was shown to exhibit specific activity comparable to that of the natural ANF-(3-33).

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Section: Discussionmentioning

confidence: 82%

Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

Seidah¹,

Lazure²,

Chrétien³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

184

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“…Similarly, other ovine peptides were isolated and their amino acid sequences [17] can now be localized to positions 568-593 as shown in fig.4. It is worth mentioning that all these peptides, sites of proteolytic cleavage in prohormones [18]. Furthermore, Tatemoto et al [19] have described a novel porcine C-terminally amidated peptide, pancreastatin, which inhibits insulin secretion and displays a significant sequence homology to positions 261-314 of prechromogranin A [20,21].…”

Section: Discussionmentioning

confidence: 99%

“…Even more interestingly, this peptide is flanked at both COOH-and NH2-termini by pairs of basic amino acids in the chromogranin B sequence. Furthermore, we noticed that GAWK 1-74, itself, is converted into two smaller fragments, GAWK 1-17 and 20-74, following cleavage at an Arg-Arg pair occupying position [18][19].…”

Section: Introductionmentioning

confidence: 97%

Chromogranin B (secretogranin I), a putative precursor of two novel pituitary peptides through processing at paired basic residues

et al. 1987

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During the course of reversed-phase high-pressure liquid chromatography (RP-HPLC) purification of the 7B2 peptide originally isolated in our laboratory from human pituitary gland extracts, two novel peptides were identified and purified to homogeneity. The complete amino acid sequence of the first one was established in 1985 and recently found to be entirely homologous to positions 420-493 of the just published chromogranin B sequence. This peptide, denoted GAWK, could originate from chromogranin B following specific cleavage at the basic amino acids flanking both termini of GAWK. Moreover, another peptide isolated in our laboratory from the same source and denoted CCB has been discovered and its sequence is also part of the same chromogranin B molecule. Here again, this peptide, occupying positions 597-653 and located at the COOH-terminal region of chromogranin B, could derive from specific processing at basic amino acids, Arg-Lys-Lys, present at positions 594-596. In a manner reminiscent of the relationship between pancreastatin and chromogranin A, it is proposed that both GAWK and CCB are produced from chromogranin B after specific processing at basic amino acids. These data are thus in favor of a putative role ofchromogranins as precursors to potentially bioactive peptides.

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“…Lazure et al (1983) reviewed the minimal criteria that had to be met for any enzyme to qualify as PC. Their search by classical biochemical methods of purification from tissues combined with enzyme assays proved to be a long road, paved with many false leads and dead ends, including our own (Chrétien 2012, a review).…”

Section: The Discovery Of Pcsmentioning

confidence: 99%

60 YEARS OF POMC: From the prohormone theory to pro-opiomelanocortin and to proprotein convertases (PCSK1 to PCSK9)

Chrétien

Mbikay

2016

Journal of Molecular Endocrinology

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Pro-opiomelanocortin (POMC), is a polyprotein expressed in the pituitary and the brain where it is proteolytically processed into peptide hormones and neuropeptides with distinct biological activities. It is the prototype of multipotent prohormones. The prohormone theory was first suggested in 1967 when Chrétien and Li discovered γ-lipotropin and observed that (i) it was part of β-lipotropin (β-LPH), a larger polypeptide characterized 2 years earlier and (ii) its C-terminus was β-melanocyte-stimulating hormone (β-MSH). This discovery led them to propose that the lipotropins might be related biosynthetically to the biologically active β-MSH in a precursor to end product relationship. The theory was widely confirmed in subsequent years. As we celebrate the 50th anniversary of the sequencing of β-LPH, we reflect over the lessons learned from the sequencing of those proteins; we explain their extension to the larger POMC precursor; we examine how the theory of precursor endoproteolysis they inspired became relevant for vast fields in biology; and how it led, after a long and arduous search, to the novel proteolytic enzymes called proprotein convertases. This family of nine enzymes plays multifaceted functions in growth, development, metabolism, endocrine, and brain functions. Their genetics has provided many insights into health and disease. Their therapeutic targeting is foreseeable in the near future. Thus, what started five decades ago as a theory based on POMC fragments, has opened up novel and productive avenues of biological and medical research, including, for our own current interest, a highly intriguing hypocholesterolemic Gln152His PCSK9 mutation in French-Canadian families.

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Proteases and posttranslational processing of prohormones: a review

Cited by 138 publications

References 54 publications

Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

Amino acid sequence of homologous rat atrial peptides: natriuretic activity of native and synthetic forms.

Chromogranin B (secretogranin I), a putative precursor of two novel pituitary peptides through processing at paired basic residues

60 YEARS OF POMC: From the prohormone theory to pro-opiomelanocortin and to proprotein convertases (PCSK1 to PCSK9)

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