• Download Fangliang Zhang, 's CV

 

Arginylation is a posttranslational addition of arginine mediated by an enzyme, arginyltransferase1 (Ate1). This process is essentially independent of the ribosome and mRNA. By adding one extra positively charged amino acid, arginylation is capable of changing the surface charge as well as the primary sequence of a protein. Ate1 is conserved in eukaryotic organism and also found in many prokaryotic organisms. Mounting evidence suggested that Ate1 (and arginylation) is involved in embryo development, immune response, and pathogenesis of cardiovascular diseases and cancers. However, the underlying molecular mechanism is extremely poorly understood. Currently, there are less than 10 labs in the world with demonstrated expertise working with this phenomenon.

Our lab is currently investigating these following topics:

1. Proteolytic processing and posttranslational arginylation of cytoskeletal proteins in relation to cellular adhesions

2. The role of arginylation and Ate1 in mitochondria and stress response in relation to cancer and other diseases

3. Molecular mechanism of arginylation and its interaction with other posttranslational modifications

We use a combination of in vitro and in vivo methods and a variety of test models including yeast, mammalian cells and mice, in our studies. We also directly test human samples for the translational aspect of our works.

• Zhang F, Saha S, Kashina A. Arginylation-dependent regulation of a proteolytic product of talin is essential for cell-cell adhesion. J Cell Biol 2012 Jun 11;197(6):819-36.
• Zhang F, Saha S, Shabalina S, Kashina A. Differential arginylation of actin isoforms is regulated by coding-sequence-dependent degradation. Science 2010, Sep 17;329(5998):1534
• Zhang F *, Patel D*, Colavita K, Rodionova I, Buckley B, Scott D, Kumar A, Shabalina SA, Saha S, Chernov M, Osterman A, Kashina A. (*Equal contribution) Arginylation regulates purine nucleotide biosynthesis by enhancing the activity of phosphoribosyl pyrophospate synthase. Nat Commun. 2015 Jul 15;6:7517. doi: 10.1038/ncomms8517. PMID: 26175007
• Rai R*, Zhang F*, Colavita K, Leu NA, Kurosaka S, Kumar A, Birnbaum MD, Gyorffy B, Dong DW, Shtutman M, Kashina A. (* Equal contribution) Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers. . Oncogene. 2016 Aug 4;35(31):4058-68. doi: 10.1038/onc.2015.473. Epub 2015 Dec 2
• Kumar A, Birnbaum MD, Patel DM, Morgan WM, Singh J, Barrientos A, Zhang F. Posttranslational arginylation enzyme Ate1 affects DNA mutagenesis by regulating stress response. Cell Death and Disease (2016) 7, e2378; doi:10.1038/cddis.2016.284
• Link for additional publications on my Pubmed profile

Through my training and research experience, I have developed a multi-disciplinary expertise. I was trained as a biochemist by an enzymologist Dr. Daniel Purich at the University of Florida. In my first postdoctoral position, I was trained by Dr. John Murray at the University of Pennsylvania to learn cutting-edge skills in electron microscopy and optical imaging. In my second postdoctoral experience I was working with Dr. Anna Kashina at the University of Pennsylvania to use both my skills in biochemistry and cell biology in studying posttranslational arginylation.

My own laboratory’s major focus is the effects of posttranslational modifications ((including arginylation, acetylation, ubiquitination, and proteolysis) on cellular behaviors such as cell adhesion/migration, stress response and programmed cell death. Particularly, our lab is one of the very few places in the world (probably less than 10) that have demonstrated expertise in studying arginylation. Our research topic is a multidisciplinary topic at the interface between biochemistry, cell biology and developmental biology. We are particularly interested in elucidating the role of posttranslational arginylation in regulating cell contact inhibition in the culture, and progression of prostate cancers in human patients.

Our lab is funded by a R01 from NIH/NIGMS, and several other grants from DoD/CDMRP, the Sylvester Cancer Center and other resources.