High impact information on MKRN1

• Furthermore, we have used the yeast two-hybrid method to identify a novel RING finger gene (MKRN1) encoding an E3 ligase that mediates ubiquitination of hTERT [1].
• Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT [1].
• This places the gene duplication event that created this locus from an ancestral MKRN1 gene early in vertebrate evolution, over 450 million years ago [2].
• In addition, truncation of either the amino- or carboxy-terminal half of MKRN1 disrupts its transactivation activity, the same observation that was made on its transrepression activity [3].
• Surprisingly, when fused to the heterologous DNAbinding domain of GAL4, MKRN1 activates, rather than inhibits, a GAL4-responsive reporter plasmid [3].

Biological context of MKRN1

• Our data suggest that MKRN1 plays an important role in modulating telomere length homeostasis through a dynamic balance involving hTERT protein stability [1].
• Phylogenetic analysis supports a model of poxviral capture of a MKRN cDNA and fusion with an existing viral gene [4].
• Recently identified avipox N1R/p28 orthologues further encode additional Makorin-like zinc-finger motifs, consistent with this suggestion [4].

Associations of MKRN1 with chemical compounds

• Overexpression of MKRN1 in mammalian cells inhibited the transcriptional activities of not only c-Jun, but also the nuclear receptors, the androgen receptor, and the retinoic acid receptors [3].

Other interactions of MKRN1

• Thus, MKRN1 may represent a nuclear protein with multiple nuclear functions, including regulating RNA polymerase II-catalyzed transcription [3].

References