Human Spot 14 protein is a p53-dependent transcriptional coactivator via the recruitment of thyroid receptor and Zac1.
Spot 14 is an acidic homodimeric protein with no sequence similarity to other mammalian gene products. Its biochemical function remains unclear. Recent studies have shown that the human Spot 14 locus is in the chromosomal region 11q13 and is frequently amplified in breast cancers, suggesting that it plays a role in the gene regulation involved in cell growth during tumorigenesis. Our previous work has demonstrated that human Spot 14 protein physically and functionally interacts with thyroid receptor in the regulation of malic enzyme gene expression. In this study, we investigated the subcellular distribution of human Spot 14 protein using enhanced green fluorescence protein and infer that its localization might be affected by thyroid hormone. Our results also demonstrate that the potential transactivation activity of human Spot 14 protein is regulated by its C-terminal region. Human Spot 14 protein is involved both in the regulation of malic enzyme promoter activity, and in the regulation of p53-dependent transactivation. It does not interact directly with p53, whereas it is able to directly interact with thyroid receptor and Zac1 (zinc finger protein which regulates apoptosis and cell cycle arrest 1) using glutathione-S-transferase pull-down assay. Hence, human Spot 14 protein might regulate the p53 target gene, p21(WAF1/Cip1), via its direct interaction with the thyroid receptor or other p53 coactivators, such as Zac1. These findings provide a molecular rationale for the role of human Spot 14 protein in the p53-dependent transcriptional activation of specific genes via diverse pathways in cells.
Chou
Wei-Yuan
WY
Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan, ROC.
Ho
Ching-Liang
CL
Tseng
Mei-Ling
ML
Liu
Shu-Ting
ST
Yen
Li-Chen
LC
Huang
Shih-Ming
SM
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C106464:PLAGL1 protein, human; D011988:Receptors, Thyroid Hormone; C051065:THRSP protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014284:Triiodothyronine