Chung, Bon-chu
Function and Regulation of Steroid Hormone Synthesis
We have been studying the functions of steroid hormones and the regulation of their synthesis. A key enzyme in the steroid synthetic pathway, cytochrome P450scc, is encoded by CYP11A, which is expressed in the adrenal cortex and gonads activated by transcription factor SF-1 (NR5A1). Three different aspects of steroid regulation have been the focus of our investigation.
I. Mechanism regulating function of SF-1
We have investigated the mechanism that controls SF-1 activation of CYP11A1 transcription in response to cAMP, and found HIPK3 essential via the phosphorylation of JNK and c-Jun. In addition, we find that SF-1 can be modified by ubiquitination, acetylation and sumoylation, which further modulate SF-1 action. The physiological significance of the interplay among these molecules and their nuclear location is under extensive investigation.
II. Steroid Function and Regulation in Mouse
We have established mouse models with targeted Cyp11a1 gene disruption. The Cyp11a1 mutant mice are defective in steroid synthesis, forming the basis for the study of steroid functions in sexual development, energy balance, and stress response.
III. Steroid Function and Regulation in Zebrafish Development
We have studied zebrafish steroidogenic gene functions by knocking down gene expression using antisense morpholino oligos. This results in defects at various stages of development, revealing new functions of steroids in gastrulation, cell migration and tissue differentiation during embryogenesis.
Selected Recent Publications:
- Huang S-C, Lee C-t, Chung B-c, "Tumor Necrosis Factor Suppresses NR5A2 Activity and Intestinal Glucocorticoid Synthesis to Sustain Chronic Colitis" Sci. Signal., 7 (314), ra20, 1-11 [DOI: 10.1126/scisignal.2004786] (2014).
- Weng J-H, Liang M-R, Chen C-H, Tong S-K, Huang T-C, Lee S-P, Chen Y-R, Chen C-T, and Chung B-c, "Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration" Nature Chem Biol, 9, 636-642 (2013). (cover picture)
- Yu C, Cheng W-C, Wu M-R, Jiang S-T, Shen C-KJ, Chung B-c, "Mis-regulated Progesterone Secretion and Impaired Pregnancy in Cyp11a1 Transgenic Mice" Biol Reprod, 89 (4) 91, 1-10 (2013). (Recommended by Faculty of 1000 Prime)
- Wang C-Y, Kao Y-H, Lai P-Y, Chen W-Y, and Chung B-c, "Steroidogenic Factor-1 (NR5A1) Maintains Centrosome Homeostasis in Steroidogenic Cells by Restricting Centrosomal DNA-PK Activation" Mol Cell Biol, 33, 476-484 (2013).
- Lan H-S, Wu C-F, Shih H-M, and Chung B-c, "Death-Associated Protein 6 (Daxx) Mediates cAMP-Dependent Stimulation of Cyp11a1 (P450scc) Transcription" J Biol Chem 287, 5910–5916 (2012).