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
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.
- 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:|
Kun-Han Chuang (Postdoctoral fellow)
Michael Bokros (Graduate Student)
Ryan Higgins (Graduate Student)
Dr. Fengzhi Jin (Assistant Scholar Scientist)
Kelly McKnight (Recently graduated)
Curtis Gravenmier (Undergraduate Student)
Current Members from Left to Right: Fengzhi Jin, Michael Bokros, Curtis Gravenmier, Ryan Higgins, Kelly McKnight, Kun-Han Chuang, Yanchang Wang.
- Jin F., Liu H., Liang F., Rizkallah R., Hurt M. and Wang Y. (2008) Temporal control of the dephosphorylation of Cdk substrates by mitotic exit pathways in budding yeast. Proc Natl Acad Sci U S A. 105:16177-82.
- Liu H., Liang F., Jin F. and Wang Y. (2008) The coordination of centromere replication, spindle formation and kinetochore-microtubule interaction in budding yeast. PLoS Genetics. Nov.4:e1000262. Epub 2008 Nov 21.
- Liang F., Jin F., Liu H. and Wang Y. (2009) The molecular function of the yeast polo-like kinase Cdc5 in Cdc14 release during early anaphase. Mol. Biol Cell 20:3671-3679.
- Liu, H., Jin, F., Liang, F., Tian, X., and Wang, Y. (2011). The Cik1/Kar3 Motor Complex Is Required for the Proper Kinetochore-Microtubule Interaction After Stressful DNA Replication. Genetics, 187(2), 397-U58.
- Jin F., Liu H., Li P., Yu H-G, 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.
- Lin Y., Li Y., Zhu Y., Zhang J., Li Y., Liu X., Jiang W., Yu S., You X., Xiao C., Hong B., Wang Y.*, Jiang J-D*, 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).
- 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 (cover image).
- 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.
- Jin F. and Wang Y. (2013) The signaling network that silencing the spindle assembly checkpoint upon the establishment of chromosome bipolar attachment. Proc Natl Acad Sci U S A 110:21036-41.
- Lin Y, Li Y, Zhu N, Han Y, Jiang W, Wang Y, Si S, Jiang J. (2014) The anti-tuberculosis antibiotic capreomycin inhibits protein synthesis through disrupting interaction between ribosomal proteins L12 and L10. Antimicrob Agents Chemother 58:2038-44.
- McKnight K, Liu H, and Wang Y. (2014) Replicative stress induces intragenic transcription of the ASE1 gene that negatively regulates Ase1 activity. Current Biology (in press).
- Wang Y, Jin F, Higgins R, and McKnight K. (2014) The current view of the silencing of the spindle assembly checkpoint. Cell Cycle (in press).