Abstract
When I became a physician and an endocrinologist in the early 1960s, peptide hormone sequencing was still in its infancy; it was also far removed from my immediate interests. Through chance encounters with prominent teachers and mentors, I later became increasingly convinced that elucidation of the primary sequence of peptide hormones is key to understanding their production as well as their functions in human health and disease. My interest for pituitary hormones led me to discover that the sequence of β-melanocyte-stimulating hormone was contained within that γ and β-lipotropins and could be released from the latter by limited endoproteolysis. This prohormone theory became the leitmotiv of my career as a clinician/scientist. Through serendipity and the efforts of many laboratories including mine, this theory has now been widely confirmed, extended to various precursor proteins and implicated in many diseases. It has led to our discovery of the proprotein convertases.
“Dans les champs de l’observation, la chance sourit aux esprits préparés.”
(In the field of observation, chance favors the prepared mind).
Louis Pasteur (1822–1895)
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References
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Acknowledgments
Serendipity in my career would not have become rewarding opportunities without the guidance of my mentors Dr Jacques Genest, Dr Roger Boucher, Dr John S.L. Browne, and Dr Arthur Gagnon in Montréal; Dr George Thorn and Dr George Cahill in Boston; Dr Choh Hao Li, Dr John Ramachandran, Dr Jon Dixon and David Chung at the University of California at San Francisco and Berkeley. I am deeply indebted to my long-time and closest collaborators Dr Nabil G. Seidah, Mrs Suzanne Benjannet, and Dr Majambu Mbikay. Over the years, we were joined by many others: Drs Claude Lazure, Ajoy Basak, Annik Prat, Mycieslaw Marcinkiewicz, Martin Lis, Robert Day, Abdel-Majid Khatib, and Janice Mayne. All along, I benefited from the administrative support of three skillful and devoted assistants: Mmes Diane Marcil, Sylvie Émond, and Denise Joanisse. Many post-doctoral fellows or then-graduate students have made invaluable contributions to our research: alphabetically by last name, Drs Younes Anini, Xavier Bertagna, Guy Boileau, Peter Burbach, John Chan, Gilles Croissandeau, Philippe Crine, Michael Dennis, Christina Gianoulakis, François Gilbert, Francis Gossard, Kuo Liang Hsi, Haruo Iguchi, François Jean, Guy Lambert, Normand Larivière, Richard Leduc, Chao Lin Lu, Rami Morcos, Joanne Paquin, Didier Pélaprat, Marie-Laure Raffin-Sanson Hélène Scherrer, Glen Smith, Philipp Stawowy, and Philippe Touraine. Some devoted technicians have worked with us for decades: Jim Rochemont, Andrew Chen, Francine Sirois, Odette Théberge, Marie-Claude Guérinot, and Josée Hamelin.
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Chrétien, M. (2011). The Prohormone Theory and the Proprotein Convertases: It Is All About Serendipity. In: Mbikay, M., Seidah, N. (eds) Proprotein Convertases. Methods in Molecular Biology, vol 768. Humana Press. https://doi.org/10.1007/978-1-61779-204-5_2
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DOI: https://doi.org/10.1007/978-1-61779-204-5_2
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