The nuclear localization of SOCS6 requires the N-terminal region and negatively regulates Stat3 protein levels.
We determined that endogenous- and overexpressed- SOCS6 was localized in both the nucleus and cytoplasm. The localization of SOCS6 depended on amino acids 1-210 in the N-terminal region of the protein, which contains an unidentified domain. GFP-tagged SOCS6 or the N-terminal region, was exclusively localized and widely distributed throughout the entire nucleus, whereas the C-terminal region displayed a nuclear omission pattern. We also demonstrated that the SOCS6 protein could decrease the levels of the Stat3 protein in the nucleus, and that its negative regulation of the Stat3 protein level was dependent on its C-terminal region. These observations suggest that SOCS6 is composed of at least two functional domains required for its biological role in localizing and degrading Stat3 in the nucleus.
Hwang
Mi-Na
MN
Research Institute, National Cancer Center, 809 Madu l-dong, Ilsan-gu, Goyang-si Gyeonggi-do 411-764, Republic of Korea.
Min
Chan-Hee
CH
Kim
Hyung Sik
HS
Lee
Ho
H
Yoon
Kyong-Ah
KA
Park
Sung Yong
SY
Lee
Eun Sook
ES
Yoon
Sungpil
S
D002467:Cell Nucleus / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D050796:STAT3 Transcription Factor / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry* / Q000378:metabolism*
C473085:SOCS6 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050826:Suppressor of Cytokine Signaling Proteins