Evolutionary Conservation of MKRN3 and Other Makorins and Their Roles in Puberty Initiation and Endocrine Functions

• Published in: Seminars in reproductive medicine Vol. 37; no. 4; p. 166
• Main Authors: Naulé, Lydie, Kaiser, Ursula B
• Format: Journal Article
• Language: English
• Published: United States 01-07-2019
• Subjects: Animals; Conserved Sequence; Endocrine System - physiology; Evolution, Molecular; Humans; Puberty - genetics; Ribonucleoproteins - genetics; Ribonucleoproteins - physiology; Sexual Maturation - genetics; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - physiology
• ISSN: 1526-4564
• DOI: 10.1055/s-0039-3400965

Puberty is a critical period of development regulated by genetic, nutritional, and environmental factors. The role of
(
) in the regulation of pubertal timing was revealed when loss-of-function mutations were identified in patients with central precocious puberty (CPP). To date,
mutations are the most common known genetic cause of CPP. MKRN3 is a member of the makorin family of ubiquitin ligases, together with MKRN1 and MKRN2. The
genes have been identified in both vertebrates and invertebrates and show high evolutionary conservation of their gene and protein structures. While the existence of Mkrn orthologues in a wide spectrum of species suggests a vital cellular role of the makorins, their role in puberty initiation and endocrine functions is just beginning to be investigated. In this review, we discuss recent studies that have shown the involvement of Mkrn3 and other makorins in the regulation of pubertal development and other endocrine functions, including metabolism and fertility, as well as their underlying mechanisms of action.