NEMO stabilizes c-Myc through direct interaction in the nucleus.
The transcription factor c-Myc is a cellular oncoprotein generally upregulated in most of human cancers. NF-κB essential modulator (NEMO) caused phosphorylation and stabilization of c-Myc protein in the nucleus through direct interaction. The interaction caused reduced ubiquitination of c-Myc by inhibiting ubiquitinating activity of Fbw7 without blocking the interaction between c-Myc and Fbw7. As a consequence, NEMO enhanced the expression of several selected c-Myc targets. Compared to the classical role as an essential subunit for the activity of IKK complex, stabilization of c-Myc by direct interaction is a unique function of NEMO, representing a new mechanism to regulate c-Myc activity.
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
Bu-Yeon
BY
Kim
Ji-Sook
JS
Yang
Seo-Young
SY
Kwak
Xiao-kun
XK
Zhang
Young-Hoon
YH
Han
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D055550:Protein Stability; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D016271:Proto-Oncogene Proteins c-myc