Human spot 14 protein interacts physically and functionally with the thyroid receptor.
Spot 14 (S14) is a small acidic protein with no sequence similarity to other mammalian gene products. Its biochemical function is elusive. Recent studies have shown that, in some cancers, human S14 (hS14) localizes to the nucleus and is amplified, suggesting that it plays a role in the regulation of lipogenic enzymes during tumorigenesis. In this study, we purified untagged hS14 protein and then demonstrated, using various biochemical methods, including analytic ultracentrifugation, that hS14 might form a homodimer. We also found several lines of evidence to suggest physical and functional interactions between hS14 and the thyroid hormone receptor (TR). The ubiquitous expression of hS14 in various cell lines and its cell-type-dependent functions demonstrated in this study suggest that it acts as a positive or negative cofactor of the TR to regulate malic enzyme gene expression. These findings provide a molecular rationale for the role of hS14 in TR-dependent transcriptional activation of the expression of specific genes.
Chou
Wei-Yuan
WY
Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC.
Cheng
Yi-Shan
YS
Ho
Ching-Liang
CL
Liu
Shu-Ting
ST
Liu
Pei-Yao
PY
Kuo
Chen-Chin
CC
Chang
Hui-Ping
HP
Chen
Yu-Hou
YH
Chang
Gu-Gang
GG
Huang
Shih-Ming
SM
D002460:Cell Line; D006801:Humans; D008291:Malate Dehydrogenase / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D009687:Nuclear Proteins; D011988:Receptors, Thyroid Hormone; C051065:THRSP protein, human; D014157:Transcription Factors; D008291:Malate Dehydrogenase; C495394:malic enzyme 2; human