RNF122: a novel ubiquitin ligase associated with calcium-modulating cyclophilin ligand.
BACKGROUND
RNF122 is a recently discovered RING finger protein that is associated with HEK293T cell viability and is overexpressed in anaplastic thyroid cancer cells. RNF122 owns a RING finger domain in C terminus and transmembrane domain in N terminus. However, the biological mechanism underlying RNF122 action remains unknown.


RESULTS
In this study, we characterized RNF122 both biochemically and intracellularly in order to gain an understanding of its biological role. RNF122 was identified as a new ubiquitin ligase that can ubiquitinate itself and undergoes degradation in a RING finger-dependent manner. From a yeast two-hybrid screen, we identified calcium-modulating cyclophilin ligand (CAML) as an RNF122-interacting protein. To examine the interaction between CAML and RNF122, we performed co-immunoprecipitation and colocalization experiments using intact cells. What is more, we found that CAML is not a substrate of ubiquitin ligase RNF122, but that, instead, it stabilizes RNF122.


CONCLUSIONS
RNF122 can be characterized as a C3H2C3-type RING finger-containing E3 ubiquitin ligase localized to the ER. RNF122 promotes its own degradation in a RING finger-and proteasome-dependent manner. RNF122 interacts with CAML, and its E3 ubiquitin ligase activity was noted to be dependent on the RING finger domain.
Peng
Zhi
Z
Chinese National Human Genome Center, #3-707 North YongChang Road BDA, Beijing 100176, PR China.
Shi
Taiping
T
Ma
Dalong
D
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D054829:RING Finger Domains / Q000235:genetics; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C089404:CAMLG protein, human; D008024:Ligands; D008565:Membrane Proteins; C529404:ring finger protein 122, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex