We are interested in the following questions:
- How do translational modifications regulate PML function?
- How do the post-translational modifications of PML cross-talk with each other?
- How do PML target genes mediate its cellular function?
Our lab is interested in transcriptional regulation in human health and diseases. Currently, we have two ongoing projects:
Characterizing the biological function of histone deacetylase 7 (HDAC7) and its interacting proteins including alpha actinin 4 (ACTN4)
HDAC7 is a member of class II HDACs. Precise regulation of the subcellular distribution of class II HDACs plays a pivotal role in cell differentiation and animal development. ACTN4 is an HDAC7 interacting protein and mutations in ACTN4 are associated with focal segmental glomerulosclerosis (FSGS), a kidney disease characterized by proteinuria. We are investigating the function and regulation of HDAC7 and ACTN4 in endothelial cells and podocytes.
Investigating the function and regulation of promyelocytic leukemia protein (PML).
PML is a tumor suppressor protein that control many cellular processes including apoptosis, cell proliferation, senescence, and transcription. PML is subjected to several post-translational modifications such as phosphorylation, sumoylation, acetylation, ubiquitination, and isgylation.
- Huang W., Peng Y., Kiselar J., Zhao X., Albaqami A., Mendez D., Chen Y., Chakravarthy S., Gupta S., Ralston C., Kao H.Y., Chance M.R., Yang S.
“Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains.”
Nat Commun. 30;9(1):3520(2018).
- Zhang Y. Y., Tabataba H., Liu X. Y., Wang J. Y., Yan X. G., Farrelly M., Jiang C. C., Guo S. T., Liu T., Kao H. Y., Thorne R. F., Zhang X. D., and Jin L.
“ACTN4 regulates the stability of RIPK1 in melanoma”
Oncogene 37 (29): 4033-45 (2018).
- Pan S. C., Li C. Y., Kuo C. Y., Kuo Y. Z., Fang W. Y., Huang Y. H., Hsieh T. C., Kao H. Y., Kuo Y., Kang Y. R., Tsai W. C., Tsai S. T., and Wu L. W.
“The p53-S100A2 Positive Feedback Loop Negatively Regulates Epithelialization in Cutaneous Wound Healing”
Sci Rep 8 (1): 5458 (2018).
- Hsu K. S. and Kao H. Y.
“PML: Regulation and multifaceted function beyond tumor suppression”
Cell Biosci 8: 5 (2018).
- Zhao X., Khurana S., Charkraborty S., Tian Y., Sedor J. R., Bruggman L. A., and Kao H. Y.
“alpha Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes”
J Biol Chem 292 (5): 1637-47 (2017).
- Hsu K. S., Zhao X., Cheng X., Guan D., Mahabeleshwar G. H., Liu Y., Borden E., Jain M. K., and Kao H. Y.
“Dual regulation of Stat1 and Stat3 by the tumor suppressor protein PML contributes to interferon alpha-mediated inhibition of angiogenesis”
J Biol Chem 292 (24): 10048-60 (2017).
- Hsu K. S., Guan B. J., Cheng X., Guan D., Lam M., Hatzoglou M., and Kao H. Y.
“Translational control of PML contributes to TNFalpha-induced apoptosis of MCF7 breast cancer cells and decreased angiogenesis in HUVECs”
Cell Death Differ 23 (3): 469-83 (2016).
- Zhao X., Hsu K. S., Lim J. H., Bruggeman L. A., and Kao H. Y.
“alpha-Actinin 4 potentiates nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-kappaB) activity in podocytes independent of its cytoplasmic actin binding function”
J Biol Chem 290 (1): 338-49 (2015).
- Lim L. M., Zhao X., Chao M. C., Chang J. M., Chang W. C., Kao H. Y., Hwang D. Y., and Chen H. C.
“Novel Vitamin D Receptor Mutations in Hereditary Vitamin D Resistant Rickets in Chinese”
PLoS One 10 (9): e0138152 (2015).
- Kao H. Y.
“The actinin family proteins: biological function and clinical implications”
Cell Biosci 5: 48 (2015).
- Guan D. and Kao H. Y.
“The function, regulation and therapeutic implications of the tumor suppressor protein, PML”
Cell Biosci 5: 60 (2015).
- Guan D., Lim J. H., Peng L., Liu Y., Lam M., Seto E., and Kao H. Y.
“Deacetylation of the tumor suppressor protein PML regulates hydrogen peroxide-induced cell death”
Cell Death Dis 5: e1340 (2014).
- Guo S., Cheng X., Lim J. H., Liu Y., and Kao H. Y.
“Control of antioxidative response by the tumor suppressor protein PML through regulating Nrf2 activity”
Mol Biol Cell 25 (16): 2485-98 (2014).