Makorin RING finger protein 1 (MKRN1) has negative and positive effects on RNA polymerase II-dependent transcription.
Through its transcriptional activities, the proto-oncoprotein c-Jun can regulate cellular proliferation, survival, and differentiation. We have established a novel yeast assay that screens for repressors of c-Jun transcriptional activity. This screen led to the identification of a ubiquitously expressed novel RING zinc finger protein, termed Makorin RING zinc finger protein 1 (MKRN1), recently shown to act as an E3 ubiquitin ligase. 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. Truncation analysis indicates that both the amino and carboxy termini are required for this transrepression activity. Surprisingly, when fused to the heterologous DNAbinding domain of GAL4, MKRN1 activates, rather than inhibits, a GAL4-responsive reporter plasmid. 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. These results demonstrate that MKRN1 has transcriptional activity and suggest that its transrepression and transactivation functions are mediated by the same mechanism. Interestingly, disruption of MKRN1's ubiquitin ligase activity does not affect its inhibitory transcriptional activity. Thus, MKRN1 may represent a nuclear protein with multiple nuclear functions, including regulating RNA polymerase II-catalyzed transcription.
Omwancha
Josephat
J
Department of Biological Sciences, University of Toledo, OH 43606, USA.
Zhou
Xiao-Feng
XF
Chen
Shao-Yong
SY
Baslan
Timour
T
Fisher
Christopher J
CJ
Zheng
Zhe
Z
Cai
Changmeng
C
Shemshedini
Lirim
L
D000818:Animals; D000941:Antigens / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors; D012261:Ribonucleoproteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D000941:Antigens; D004268:DNA-Binding Proteins; C410808:Makorin ring finger protein 1; D009419:Nerve Tissue Proteins; D016755:Proto-Oncogene Proteins c-jun; D018168:Receptors, Retinoic Acid; D012261:Ribonucleoproteins; D018808:Transcription Factor AP-1; C026908:ubiquitous tissue antigen; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II