Xiao, Wei

Professor

Wei Xiao

Department of Biochemistry, Microbiology and Immunology
University of Saskatchewan, 107 Wiggins Road
Saskatoon, Saskatchewan, Canada
S7N 5E5

Phone: 306-966-4308

Email: wei.xiao@usask.ca

Website: http://homepage.usask.ca/~wex973/wex973/Home.html


Academic Degrees

  • B.Sc. (1982) Nanjing Agricultural University
  • M.Sc. (1984) University of Toronto
  • Ph.D. (1988) University of Saskatchewan
  • PDF (1990-1992) Harvard University

Current Teaching

  • MCIM 391.3  Experimental Molecular Microbiology
  • MCIM 816.3  Genetic Analysis of Eukaryotic Microorganisms
  • MCIM 820.3  DNA Repair and Mutagenesis

Current and Recent Research Projects

Ubiquitin (Ub) is an abundant, ubiquitous and highly-conserved small protein (76 amino acids) found in all eukaryotic cells, from unicellular yeasts to human. Through a series of enzymatic reactions, Ub is attached to the target protein with the help of an Ub conjugating enzyme (E2 or Ubc) and an Ub ligase (E3), followed by the formation of a multimeric Ub chain known as the poly-Ub chain. Target proteins attached by poly-Ub are sent for degradation by the 26S proteosome, and this process serves as an important means of regulation involved in numerous cellular activities. Its importance is appreciated by the 2004 Nobel Prize award to the discovery of ubiquitination and its involvement in the target protein degradation. Careful investigation reveals that the above Ub chain is formed via a surface Lys48 residue of an incoming Ub attached to the C-terminal Gly residue. It was subsequently found that the Ub chain can also be formed via a surface Lys63 residue. Among over a dozen of Ubcs found in any organisms, only one, Ubc13, is capable of linking Ub through Lys63. The unique feature of Ubc13 is due to its binding to another protein known as Uev (Ubc enzyme variant), which is also absolutely required for the process. More importantly, proteins attached by Lys63-linked Ub are not targeted for degradation, but for altering activities. Furthermore, among other types of ubiquitination, mono-ubiquitination is also believed to be a novel regulatory mechanism of the target protein activity, which expands the horizon of ubiquitination functions. My laboratory is primarily interested in the discovery of above non-conventional ubiquitinaiton processes and in defining the molecular mechanisms of the related pathways. Since a few well characterized non-conventional ubiquitination target proteins are involved in cellular metabolisms such as DNA damage tolerance, cell cycle checkpoint, innate immunity and stress response, and that these processes play critical roles in human diseases like cancer, this study will have direct impacts on the diagnosis and treatment of diseases including cancer.


Publications

Rout, M.K., Lee, B.L., Lin, A., Xiao, W. and Spyracopoulos, L. (2018) Active site gate dynamics modulate the catalytic activity of the ubiquitination enzyme E2-25K. Sci. Rep. 8: 7002.

Wu, Z., Neufeld, H., Torlakovic, E. and Xiao, W. (2018) Uev1A-Ubc13 promotes colorectal cancer metastasis through regulating CXCL1 expression via NF-кB activation. Oncotarget 9: 15952-15967. 

Li, Z., Wang, Y., Li, Y., Zhang, Y., Zhang, Z., Ren, X., Yin, W., Wang, G., Zhu, B., Xiao, W. and Zhang, W. (2018) Ube2s stabilizes β-Catenin through K11-linked polyubiquitination to promote mesendoderm specification and colorectal cancer development. Cell Death & Disease 9: 456.

Zhao, H., Wang, Q., Liu, C., Shang, Y., Wen, F., Wang, F., Liu, W., Xiao, W. and Li, W. (2018) A role for respiration in regulating meiosis initiation in Saccharomyces cerevisiae. Genetics 208: 1181-1194.

Qin, Z., Jiang, W., Wang, G., Sun, Y. and Xiao, W. (2018) Linear ubiquitin chain induces apoptosis and inhibits tumor growth. Apoptosis 23: 16-26.

Zhang, Y., Li, Y., Yang, X., Wang, J., Wang, R., Qian, X., Zhang, W. and Xiao, W. (2018) Uev1A-Ubc13 catalyzes K63-linked ubiquitination of RHBDF2 to promote TACE maturation. Cell. Signal. 42: 155-164.

Niu, C., Wang, D., Liu, X., Liu, H., Liu, X., Feng, E., Pan, C., Wang, R., Xiao, W., Liu, X., Liu, X., Zhu, L. and Wang, H. (2017) An H-NS family protein, Sfh, regulates acid resistance by inhibition of glutamate decarboxylase expression in Shigella flexneri 2457T. Front. Microbiol. 8: 1923.

Zhang, W., Zhuang, Y., Zhang, Y., Yang, X., Zhang, H., Wang, G., Yin, W., Wang, R., Zhang, Z. and Xiao, W. (2017) Uev1A facilitates osteosarcoma differentiation by promoting Smurf1-mediated Smad1 ubiquitination and degradation. Cell Death & Diseases 8: e2974. 

Bhat, A., Qin, Z., Wang, G., Chen, W. and Xiao, W. (2017) Rev7, the regulatory subunit of Polζ, undergoes UV-induced and Cul4-dependent degradation. FEBS J. 284: 1790-1803. (Cover and Editor’s Choice for issue 12, and is included in a special annual highlights virtual issue). 

Niu, C., Yang, J., Liu, H., Cui, Y., Xu, H., Wang, R., Liu, X., Feng, E., Wang, D., Pan, C., Xiao, W., Liu, X., Zhu, L. and Wang, H. (2017) Role of the virulence plasmid in acid resistance of Shigella flexneri. Sci. Rep. 7: 46465.

Qin, Z., Bai, Z., Sun, Y., Niu, X. and Xiao, W. (2016) PCNA-Ub polyubiquitination inhibits cell proliferation and induces cell-cycle checkpoints. Cell Cycle 15: 3390-3401.

Fan, L. and Xiao, W. (2016) The Pol30-K196 residue plays a critical role in budding yeast DNA postreplication repair through interaction with Rad18. DNA Repair 47: 42-48.

Guo, H., Wen, R., Wang, Q., Datla, R. and Xiao, W. (2016) Three Brachypodium distachyon Uev1s promote Ubc13-mediated Lys63-linked polyubiquitination and confer different functions. Front. Plant Sci. 7: 1551.

Yuan, S., Zhang, Z., Zheng, C., Zhao, Z., Wang, Y., Feng, L., Niu, G., Wang, C., Wang, J., Feng, H., Bao, F., Hu, Y., Cao, Y., Ma, L., Wang, H., Kong, D., Xiao, W., Lin, H. and He, Y. (2016) Arabidopsis cryptochrome 1 functions in nitrogen regulation of flowering. Proc. Natl. Acad. Sci. USA 113: 7661-7666. 

Tan, S., Liu, F., Pan, X., Zang, Y., Jin, F., Zu, W., Q, X., Xiao, W. and Yin, L. (2016) CSN6, a subunit of the COP9 signalosome, is involved in early response to iron deficiency in Oryza sativa. Sci. Rep. 6: 25485.

Xu, X., Lin, A., Zhou, C., Blackwell, S., Zhang, Y., Wang, Z., Feng, Q., Guan, R., Hanna, M.D., Chen, Z. and Xiao, W. (2016) Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1. Nucleic Acids Res. 44: 5231-5245.

Wang, J., Zhang, Y., Hou, J., Qian, X., Zhang, H., Zhang, Z., Li, M., Wang, R., Liao, K., Wang, Y., Li, Z., Zhong, D., Wan, P., Dong, L., Liu, F., Wang, X., Wan, Y., Xiao, W. and Zhang, W. (2016) Ube2s regulates Sox2 stability and mouse ES cell maintenance. Cell Death Differ. 23: 393-404.

Guo, H., Wen, R., Liu, Z., Datla, R. and Xiao, W. (2016) Molecular cloning and functional characterization of two Brachypodium distachyon UBC13 genes whose products promote K63-linked polyubiquitination. Front. Plant Sci. 6:1222. 

Bhat, A., Wu, Z., Maher, V.M., McCormick, J.J. and Xiao, W. (2015) Rev7/Mad2B plays a critical role in the assembly of a functional mitotic spindle. Cell Cycle 14: 3929-3938. 

Li, J., Biss, M., Fu, Y., Xu, X., Moore, S. and Xiao, W. (2015) Two duplicated genes DDI2 and DDI3 in budding yeast encode a cyanamide hydratase and are induced by cyanamide. J. Biol. Chem. 290: 12664-12675.

Xu, X., Blackwell, S., Lin, A., Li, F., Qin, Z. and Xiao, W. (2015) Error-free DNA-damage tolerance in Saccharomyces cerevisiae. Mutat. Res. - Rev. 764: 43-50.

Xue, C., Liang, K., Liu, Z., Wen, R. and Xiao, W. (2015) Similarities and differences between Arabidopsis PCNA1 and PCNA2 in complementing the yeast DNA damage tolerance defect. DNA Repair 28: 28-36.

Rout, M.K., Hodge, C.D., Markin, C.J., Xu, X., Glover, J.N.M., Xiao, W. and Spyracopoulos, L. (2014) Stochastic gate dynamics regulate the catalytic activity of ubiquitination enzymes. J. Am. Chem. Soc. 136: 17446-17458.

Wen, R., Wang, S., Xiang, D., Venglat, P., Shi, X., Zang, Y., Datla, R., Xiao, W. and Wang, H. (2014) UBC13, an E2 enzyme for Lys63-linked ubiquitination, functions in root development by affecting auxin signaling and Aux/IAA protein stability. Plant J 80: 424-436.

Wu, Z., Shen, S., Zhang, Z., Zhang, W. and Xiao, W. (2014) Ubiquitin-conjugating enzyme complex Uev1A-Ubc13 promotes breast cancer metastasis through nuclear factor-κB mediated matrix metalloproteinase-1 gene regulation. Breast Cancer Res. 16: R75.

Cao, L., Tang, X., Zhang, X., Zhang, J., Tian, X., Wang, J., Xiong, M. and Xiao, W. (2014) Two-stage transcriptional reprogramming in Saccharomyces cerevisiae for optimizing ethanol production from xylose. Metab. Eng. 24: 150-159. 

Ball, L.G., Xu, X., Blackwell, S., Hanna, M.D., Lambrecht, A.D. and Xiao, W. (2014) The Rad5 helicase activity is dispensable for error-free DNA post-replication repair. DNA Repair 16: 74-83. 

Qin, Z., Lu, M., Xu, X., Hanna, M., Shiomi, N. and Xiao, W. (2013) DNA-damage tolerance mediated by PCNA•Ub fusions in human cells is dependent on Rev1 but not Polη. Nucleic Acids Res. 41: 7356-7369. 

Bhat, A., Andersen, P.L., Qin, Z. and Xiao, W. (2013) The Rev3 subunit of Polζis required for maintaining fragile site stability in human cells. Nucleic Acids Res. 41: 2328-2339.

Wei, T., Zhang, C., Xu, X., Hanna, M., Zhang, X., Wang, Y., Dai, H. and Xiao, W. (2013) Construction and evaluation of two biosensors based on yeast transcriptional response to genotoxic chemicals. Biosensors and Bioelectronics. 44: 138-145. 

Wen, R., Li, J., Xu, X., Cui, Z. and Xiao, W. (2012) Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53-mediated DNA-damage response. DNA Repair 11: 157-166.

Xiang, D., Yang, H., Venglat, P., Cao, Y., Wen, R., Ren, M., Stone, S., Wang, E., Wang, H., Xiao, W., Weijers, D., Berleth, T., Laux, T., Selvaraj, G., Datla, R. (2011) POPCORN functions in the auxin pathway to regulate embryonic body plan and meristem organization in Arabidopsis.Plant Cell 23: 4348-4367.

Andersen, P.L., Xu, F., Ziola, B., McGregor, W.G. and Xiao, W. (2011) Sequential assembly of translesion DNA polymerases at UV-induced DNA damage sites. Mol. Biol. Cell22: 2373-2383. 

Wang, S., Wen, R., Shi, X., Lambrecht, A., Wang. H. and Xiao, W. (2011) RAD5A and REV3 constitute two alternative mechanisms of DNA damage tolerance in Arabidopsis. DNA Repair 10: 620-628.

Zhang, M., Zhang, C., Li, J., Hanna, M., Zhang, X., Dai, H. and Xiao, W. (2011) Inactivation of YAP1 enhances sensitivity of the yeast RNR3-lacZ genotoxicity testing system to a broad range of DNA-damaging agents. Tox. Sci120: 310-321.

Pastushok, L., Hanna, M. and Xiao, W. (2010) Constitutive fusion of ubiquitin to PCNA provides DNA damage tolerance independent of translesion polymerase activities. Nucleic Acids Res. 38: 5047-5058.

Markin, C.J., Xiao, W. and Spyracopoulos, L. (2010) Mechanism for recognition of polyubiquitin chains: balancing affinity through interplay between multivalent binding and dynamics. J. Am. Chem. Soc132: 11247-11258.

Zhang, M., Hanna, M., Li, J., Butcher, S., Dai, H. and Xiao, W. (2010) Creation of a hyperpermeable yeast strain to genotoxic agents through combined inactivation of PDR and CWP genes. Tox. Sci. 113: 401-411.

Ball, L.G., Zhang, K., Cobb, J.A., Boone, C. and Xiao, W. (2009) The yeast Shu complex couples error-free PRR to homologous recombination. Mol. Microbiol73: 89-102.

Huen, M.S.Y., Yuan, J., Yamamoto, M., Akira, S., Ashley, C., Xiao, W. and Chen, J. (2008) Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol. Cell. Biol19: 6104-6112.

Anderson, H.J., Vonarx, E.J., Pastushok, L., Nakagawa, M., Katafuchi, A., Gruz, P., Di Rubbo, A., Grice, D.M., Osmond, M.J., Sakamoto, A., Nohmi, T., Xiao, W. and Kunz, B.A. (2008) Arabidopsis thaliana Y-family DNA polymerase η catalyses translesion synthesis and interacts functionally with PCNA2. Plant J55: 895-908.

Fu, Y., Zhu, Y. Zhang, K., Yeung, M., Durocher, D. and Xiao, W. (2008) Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp. Cell 133: 601-611.

Zhang, M., Liang, Y., Zhang, X., Xu, Y., Dai, H. and Xiao, W. (2008) Deletion of yeast CWP genes enhances cell permeability to genotoxic agents. Toxicol. Sci103: 68-76.

Wen, R., Torres-Acosta, J.A., Pastushok, L., Lai, X., Pelzer, L., Wang, H. and Xiao, W. (2008) Arabidopsis UEV1D promotes lysine-63-linked polyubiquitination and is involved in DNA damage response. Plant Cell 20: 213-227.

Pelzer, L., Pastushok, L., Moraes, T., Glover, J.N.M., Ellison, M.J., Ziola, B. and Xiao, W. (2009) Biological significance of structural differences between two highly conserved Ubc variants. Biochem. Biophy. Res. Comm378: 563-568.

Fu, Y., Pastushok, L. and Xiao, W. (2008) DNA damage-induced gene expression in Saccharomyces cerevisiae.  FEMS Microbol. Rev. 32: 908-926.

Huen, M.S.Y., Yuan, J., Yamamoto, M., Akira, S., Ashley, C., Xiao, W. and Chen, J. (2008) Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly. Mol. Cell. Biol19: 6104-6112.

Anderson, H.J., Vonarx, E.J., Pastushok, L., Nakagawa, M., Katafuchi, A., Gruz, P., Di Rubbo, A., Grice, D.M., Osmond, M.J., Sakamoto, A., Nohmi, T., Xiao, W. and Kunz, B.A. (2008) Arabidopsis thaliana Y-family DNA polymerase η catalyses translesion synthesis and interacts functionally with PCNA2. Plant J55: 895-908.

Fu, Y., Zhu, Y. Zhang, K., Yeung, M., Durocher, D. and Xiao, W. (2008) Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp. Cell 133: 601-611.

Zhang, M., Liang, Y., Zhang, X., Xu, Y., Dai, H. and Xiao, W. (2008) Deletion of yeast CWP genes enhances cell permeability to genotoxic agents. Toxicol. Sci103: 68-76.

Rostek, C., Turner, E., Robbins, M., Rightnar, S., Xiao, W., Obenaus, A. and Harkness, T.A.A. (2008) Involvement of homologous recombination repair after proton-induced DNA damage. Mutagenesis 23: 119-129.

Brun, J., Chiu, R., Lockhart, K., Xiao, W., Wouters, B.G. and Gray, D.A. (2008) hMMS2 serves a redundant role in human PCNA polyubiquitination. BMC Mol. Biol9:24

Wen, R., Torres-Acosta, J.A., Pastushok, L., Lai, X., Pelzer, L., Wang, H. and Xiao, W. (2008) Arabidopsis UEV1D promotes lysine-63-linked polyubiquitination and is involved in DNA damage response. Plant Cell 20: 213-227.