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Review
. 2022 Apr 8:12:862206.
doi: 10.3389/fonc.2022.862206. eCollection 2022.

MRKNs: Gene, Functions, and Role in Disease and Infection

Tongtong Wang  1 , Wenqiang Liu  1 , Changfa Wang  1 , Xuelian Ma  2 , Muhammad Faheem Akhtar  1 , Yubao Li  1 , Liangliang Li  1
Affiliations
Review

MRKNs: Gene, Functions, and Role in Disease and Infection

Tongtong Wang et al. Front Oncol. .

Abstract

The makorin RING finger protein (MKRN) gene family encodes proteins (makorins) with a characteristic array of zinc-finger motifs present in a wide array from invertebrates to vertebrates. MKRNs (MKRN1, MKRN2, MKRN3, MKRN4) as RING finger E3 ligases that mediate substrate degradation are related with conserved RING finger domains that control multiple cellular components via the ubiquitin-proteasome system (UPS), including p53, p21, FADD, PTEN, p65, Nptx1, GLK, and some viral or bacterial proteins. MKRNs also served as diverse roles in disease, like MKRN1 in transcription regulation, metabolic disorders, and tumors; MKRN2 in testis physiology, neurogenesis, apoptosis, and mutation of MKRN2 regulation signals transduction, inflammatory responses, melanoma, and neuroblastoma; MKRN3 in central precocious puberty (CPP) therapy; and MKRN4 firstly reported as a novel E3 ligase instead of a pseudogene to contribute to systemic lupus erythematosus (SLE). Here, we systematically review advances in the gene's expression, function, and role of MKRNs orthologs in disease and pathogens infection. Further, MKRNs can be considered targets for the host's innate intracellular antiviral defenses and disease therapy.

Keywords: disease; infection; makorin RING finger protein (MKRN); regulation; role.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic gene structures of human mkrn1, mkrn2, mkrn3 and mkrn4 loci. Exons are represented as boxes. Number and locus of exons in genome are indicated.
Figure 2
Figure 2
Functional domains of human MKRN1 (MKRN1-long), MKRN2, MKRN3 and MKRN4, the transcript variants of human MKRN1 (MKRN1-short1, MKRN1-short2, MKRN1-short3) and porcine MKRN1. The makorins contain several C3H zinc finger domains (pink), a Cys-His (CH) motif (purple), a C3HC4 RING domain (red), missing C3H motif (C3HΔC) (green) and RING finger domain (RINGΔCC) (aqua).
Figure 3
Figure 3
The roles of MKRNs in cells. MKRNs (MKRN1, MKRN2, MKRN3, MKRN4) served as E3 ubiquitin ligase play a leading role in degrading many substrates and regulating several diseases. MKRN1 regulates energy metabolism, tumor suppression, viral protein or bacteria ubiquitination, and apoptosis by degrading their substrates. MKRN1 has RNA-binding functions, up-expressed to regulate the insulin signaling pathway during oogenesis and down-expressed to regulate the senescence-associated secretory phenotype (SASP). MKRN2, MKRN3, and MKRN4 also mediated substrates ubiquitination and degradation.
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