Wang Lab
Yanchang Wang, Ph.D.
Professor of Cell Biology
Department of Biomedical Sciences
College of Medicine, Florida State University
1115 West Call Street
Tallahassee, FL 32306-4300
Office: (850) 644-0402 - suite 3350H
Lab: (850) 645-2926 - suite 3320
Dr. Wang's Faculty Profile
Research Interests
Cell Cycle Regulation and Stress Response
Dissection of the spindle assembly checkpoint (SAC) silencing network, SSN It is well established that incorrect kinetochore-microtubule activates the spindle assembly checkpoint (SAC) to delay cell cycle progression, a mechanism essential for faithful segregation of sister chromatids to daughter cells. However, we know little how this activated checkpoint is silenced after cells established correct chromosome attachment to allow anaphase entry. Our lab has uncovered the SAC silencing network SSN that links chromosome bipolar attachment and anaphase onset through the modulation of the phosphorylation of a kinetochore protein. We are currently investigating the molecular mechanism governing this critical process.
The cellular response to the expression of damaged proteins Misfolded proteins can be refolded with the assistance of chaperones or degraded through the proteasome. When too much misfolded proteins are present, they aggregate and form a structure called aggresome, which not only decreases the toxicity of the misfolded proteins but also facilitates their clearance by autophagy. Failure of this process is responsible for the accumulation of unfolded proteins that causes cell death in neurodegenerative diseases. Using budding yeast as a model system, we have identified many genes involved in aggresome formation and we are investigating the molecular function of these genes in the response to the expression of unfolded proteins.
The regulation and function of the mitotic exit pathways in budding yeast The key driving force of cell cycle is cyclin dependent kinase (CDK), which is responsible for the phosphorylation many substrates during cell cycle. One research interest in this lab is to understand the temporal regulation of the dephosphorylation of these substrates during cell cycle as well as the function of these dephosphorylation events. Two signaling pathways called FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network) regulate the activity of phosphatase Cdc14 and are responsible for the reversal of CDK-dependent protein phosphorylation. Our research interest is the function of the reversal of S-phase CDK substrate in anaphase entry.
Intragenic transcription: regulation and function Our recent data indicate that some genes initiate transcription within the coding region (intragenic transcription) in response to DNA replication stress. We are interested in the regulation and function of this intragenic transcription in response to various stresses.
Using budding yeast as a model system for drug screening Budding yeast is a genetic-tractable model organism valuable for addressing some fundamental biological questions. Moreover, the well-established yeast two-hybrid system allows us to detect protein-protein interactions. IN collaboration with Dr. Shuyi Si from Chinese Academy of Medical Sciences, we are using budding yeast as a model system to screen anticancer, antibacterial, and antifungal drugs.
Current Projects
- To dissect the SAC silencing network, SSN
- To characterize the pathways required for the response to damaged proteins
- To understand the role of FEAR pathways in chromosome segregation
- To study the role of intragenic transcription in response to replication stress
Current Laboratory Members
| Postdoctoral fellow and Graduate Students: | Other Members: |
|---|---|
| Cory Haluska (Graduate Student) Delaney Sherwin (Graduate Student) Austin Folger (Graduate Student) Emily Gutierrez-Morton (Graduate Student) |
Marie-Helene Kabbaj (Research Assistant) |
Selected References
1. Bokros M, Sherwin D, Kabbaj MH, Wang Y . (2021) Yeast Fin1-PP1 dephosphorylates an Ipl1 substrate, Ndc80, to remove Bub1-Bub3 checkpoint proteins from the kinetochore during anaphase. PLoS Genetics 17:e1009592
2. Klionsky et al. (2021) Guidelines for the use and interpretation of assays for monitoring autophagy (4 th edition). Autophagy 17:1-382
3. Higgins R, Kabbaj MH, Sherwin D, Howell LA, Hatcher A, Tomko RJ, and Wang Y . (2020) The Cdc48 complex alleviates the cytotoxicity of misfolded proteins by regulating ubiquitin homeostasis. Cell Reports 32:107898
4. Sherwin D, Wang Y . (2019) The Opposing Functions of Protein Kinases and Phosphatases in Chromosome Bipolar Attachment. Int J Mol Sci . 20(24). pii: E6182. Review.
5. Higgins R, Kabbaj MH, Hatcher A, Wang Y . (2018) The absence of specific yeast heat-shock proteins leads to abnormal aggregation and compromised autophagic clearance of mutant Huntingtin proteins . PLoS One . 13:e0191490
6. Jin F, Bokros M, Wang Y . (2017) The phosphorylation of a kinetochore protein Dam1 by Aurora B/Ipl1 kinase promotes chromosome bipolar attachment in yeast. Sci Rep 7:11880
7. Jin F, Bokros M, Wang Y . (2017) Premature Silencing of the Spindle Assembly Checkpoint Is Prevented by the Bub1-H2A-Sgo1-PP2A Axis in Saccharomyces cerevisiae . Genetics 205:1169-1178.
8. Chuang KH, Liang F, Higgins R and Wang Y . (2016) Ubiq uilin/Dsk2 promotes inclusion body formation and vacuole (lysosome)-mediated disposal of mutated Huntingtin. Mol Biol Cell 27:2015-36
9. Bokros M, Gravenmier C, Jin F, Richmond D, and Wang Y . (2016) Fin1-PP1 helps clear spindle assembly checkpoint protein Bub1 from kinetochores in anaphase. Cell Reports 14:1074-85
10. McKnight K, Liu H, and Wang Y . (2014) Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity. Current Biology 24:1101-6.
11. Jin F. and Wang Y . (2013). The signaling network that silences the spindle assembly checkpoint upon the establishment of chromosome bipolar attachment. Proc Natl Acad Sci U S A. 110:21036-41
12. Xu Z, Graham K, Foote M, Liang F, Rizkallah R, Hurt M, Wang Y , Wu Y, Zhou Y. (2013) 14-3-3 targets chaperone-associated misfolded proteins to aggresomes . J. Cell Sci. 126:4173-86
13. Liang F, Richmond D, and Wang Y. (2013). The coordination of chromatid separation and spindle elongation by antagonistic activities of mitotic and S-phase CDKs. PLoS Genetics 9: e1003319
14. Richmond D, Rizkallah R, Liang F, Hurt M, and Wang Y. (2013) Slk19 clusters kinetochores and facilitates chromosome bipolar attachment. Mol. Biol. Cell 24:566-77
15. Lin Y, Li Y, Zhu Y, Zhang J, Li Y, Liu X, Jiang W, Yu S, You XF, Xiao C, Hong B, Wang Y* , Jiang JD*, and Si S* (2012) Identification of anti-tuberculosis agents that target ribosomal protein interactions using yeast two-hybrid system. Proc Natl Acad Sci U S A. 109:17412-7 (*co-corresponding author).
16. Jin F, Liu H, Li P, Yu HG, and Wang Y. (2012) Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint. PLoS Genetics 8: e1002492