REVIEW: Diversity of Molecular Functions of RNA-Binding Ubiquitin Ligases from the MKRN Protein Family

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Ekaterina A. Guseva^1,2,3,a*, Maria A. Emelianova^1,3, Vera N. Sidorova⁴, Anatoly N. Tyulpakov⁵, Olga A. Dontsova^1,2,3,6, Petr V. Sergiev^1,2,3,b

¹Center of Life Sciences, Skolkovo Institute of Science and Technology, 143025 Moscow, Russia

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

³Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia

⁴Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia

⁵Bochkov Research Centre of Medical Genetics, 115522 Moscow, Russia

⁶Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia

^* To whom correspondence should be addressed.

Received: June 17, 2024; Revised: August 12, 2024; Accepted: August 19, 2024

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Makorin RING finger protein family includes four members (MKRN1, MKRN2, MKRN3, and MKRN4) that belong to E3 ubiquitin ligases and play a key role in various biological processes, such as cell survival, cell differentiation, and innate and adaptive immunity. MKRN1 contributes to the tumor growth suppression, energy metabolism, anti-pathogen defense, and apoptosis and has a broad variety of targets, including hTERT, APC, FADD, p21, and various viral proteins. MKRN2 regulates cell proliferation, inflammatory response; its targets are p65, PKM2, STAT1, and other proteins. MKRN3 is a master regulator of puberty timing; it controls the levels of gonadotropin-releasing hormone in the arcuate nucleus neurons. MKRN4 is the least studied member of the MKRN protein family, however, it is known to contribute to the T cell activation by ubiquitination of serine/threonine kinase MAP4K3. Proteins of the MKRN family are associated with the development of numerous diseases, for example, systemic lupus erythematosus, central precocious puberty, Prader–Willi syndrome, degenerative lumbar spinal stenosis, inflammation, and cancer. In this review, we discuss the functional roles of all members of the MKRN protein family and their involvement in the development of diseases.

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KEY WORDS: E3 ubiquitin ligase, RING finger proteins, MKRN, makorins, RNA-binding ubiquitin ligase, central precocious puberty, systemic lupus erythematosus, tumor suppressors

DOI: 10.1134/S0006297924090037

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