Robert <span>J.</span> Deschenes, PhD

Robert J. Deschenes, PhD


We plan to use a combination of genetics, cell biology, and biochemistry to study yeast and metazoan palmitoylation, with a focus on cancer.


    • Chemical Biology and Molecular Medicine Program

Education & Training

    • Tufts University, MS - Biochemistry
    • Purdue University, PhD - Biochemistry

Our group currently focused in two general areas. The first deals with the posttranslational modification and the subcellular localization of cancer signal transduction proteins. The second deals with stress signaling and the characterization of histidine kinases. Posttranslational modification and subcellular localization of Ras oncogene proteins. It has been known for some time that Ras undergoes posttranslational addition of lipids and this is required for subcellular localization and the signaling functions of Ras. Our interests have included protein prenylation and palmitoylation. Despite extensive characterization of protein prenylation and the development of farnesyltransferase inhibitors (FTIs), many questions remain. For example, it is not known how post-prenylation events influence Ras function. We have recently used a genetic approach, followed by biochemical characterization, to isolate a Ras palmitoyltransferase (PAT). The identification of the Ras PAT provided the handle necessary to identify putative PATs in yeast, flies, worms, mouse, and human. Some of the potential human PAT genes have been linked to human diseases. We plan to pursue studies of protein palmitoylation using a combination of genetics, cell biology, and biochemistry to study yeast and metazoan palmitoylation, with a particular focus on cancer.


  • Reddy KD, Malipeddi J, DeForte S, Pejaver V, Radivojac P, Uversky VN, Deschenes RJ. Physicochemical sequence characteristics that influence S-palmitoylation propensity. J Biomol Struct Dyn. 2017 Aug;35(11):2337-2350. Pubmedid: 27498722.
  • Beard RS, Yang X, Meegan JE, Overstreet JW, Yang CG, Elliott JA, Reynolds JJ, Cha BJ, Pivetti CD, Mitchell DA, Wu MH, Deschenes RJ, Yuan SY. Palmitoyl acyltransferase DHHC21 mediates endothelial dysfunction in systemic inflammatory response syndrome. Nat Commun. 2016 Sep;7:12823. Pubmedid: 27653213. Pmcid: PMC5036164.
  • Hamel LD, Lenhart BJ, Mitchell DA, Santos RG, Giulianotti MA, Deschenes RJ. Identification of Protein Palmitoylation Inhibitors from a Scaffold Ranking Library. Comb Chem High Throughput Screen. 2016;19(4):262-274. Pubmedid: 27009891. Pmcid: PMC5068503.
  • Hamel LD, Deschenes RJ, Mitchell DA. A fluorescence-based assay to monitor autopalmitoylation of zDHHC proteins applicable to high-throughput screening. Anal Biochem. 2014 Sep;460:1-8. Pubmedid: 24878334.
  • Mitchell DA, Hamel LD, Reddy KD, Farh L, Rettew LM, Sanchez PR, Deschenes RJ. Mutations in the X-linked intellectual disability gene, zDHHC9, alter autopalmitoylation activity by distinct mechanisms. J Biol Chem. 2014 Jun;289(26):18582-18592. Pubmedid: 24811172. Pmcid: PMC4140262.
  • Luongo K, Holton A, Kaushik A, Spence P, Ng B, Deschenes R, Sundaram S, Bhansali S. Microfluidic device for trapping and monitoring three dimensional multicell spheroids using electrical impedance spectroscopy. Biomicrofluidics. 2013;7(3):34108. Pubmedid: 24404028. Pmcid: PMC3689825.
  • Mitchell DA, Hamel LD, Ishizuka K, Mitchell G, Schaefer LM, Deschenes RJ. The Erf4 subunit of the yeast Ras palmitoyl acyltransferase is required for stability of the Acyl-Erf2 intermediate and palmitoyl transfer to a Ras2 substrate. J Biol Chem. 2012 Oct;287(41):34337-34348. Pubmedid: 22904317. Pmcid: PMC3464540.
  • Pedram A, Razandi M, Deschenes RJ, Levin ER. DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol Biol Cell. 2012 Jan;23(1):188-199. Pubmedid: 22031296. Pmcid: PMC3248897.
  • Vinnakota KC, Mitchell DA, Deschenes RJ, Wakatsuki T, Beard DA. Analysis of the diffusion of Ras2 in Saccharomyces cerevisiae using fluorescence recovery after photobleaching. Phys Biol. 2010 Jun;7(2):026011. Pubmedid: 20526029. Pmcid: PMC2897723.
  • Mitchell DA, Mitchell G, Ling Y, Budde C, Deschenes RJ. Mutational analysis of Saccharomyces cerevisiae Erf2 reveals a two-step reaction mechanism for protein palmitoylation by DHHC enzymes. J Biol Chem. 2010 Dec;285(49):38104-38114. Pubmedid: 20851885. Pmcid: PMC2992244.
  • Jennings BC, Nadolski MJ, Ling Y, Baker MB, Harrison ML, Deschenes RJ, Linder ME. 2-Bromopalmitate and 2-(2-hydroxy-5-nitro-benzylidene)-benzo[b]thiophen-3-one inhibit DHHC-mediated palmitoylation in vitro. J Lipid Res. 2009 Feb;50(2):233-242. Pubmedid: 18827284. Pmcid: PMC2636914.
  • Shankarnarayan S, Narang SS, Malone CL, Deschenes RJ, Fassler JS. Modulation of yeast Sln1 kinase activity by the CCW12 cell wall protein. J Biol Chem. 2008 Jan;283(4):1962-1973. Pubmedid: 18048366. Pmcid: PMC2892218.
  • Rieg T, Bundey RA, Chen Y, Deschenes G, Junger W, Insel PA, Vallon V. Mice lacking P2Y2 receptors have salt-resistant hypertension and facilitated renal Na+ and water reabsorption. FASEB J. 2007 Nov;21(13):3717-3726. Pubmedid: 17575258.
  • Linder ME, Deschenes RJ. Palmitoylation: policing protein stability and traffic. Nat Rev Mol Cell Biol. 2007 Jan;8(1):74-84. Pubmedid: 17183362.
  • Linder M, Deschenes R. Protein palmitoylation. Methods. 2006 Oct;40(2):125-126. Pubmedid: 17012023. Pmcid: PMC1899523.
  • Budde C, Schoenfish MJ, Linder ME, Deschenes RJ. Purification and characterization of recombinant protein acyltransferases. Methods. 2006 Oct;40(2):143-150. Pubmedid: 17012026. Pmcid: PMC1899524.
  • Mitchell DA, Vasudevan A, Linder ME, Deschenes RJ. Protein palmitoylation by a family of DHHC protein S-acyltransferases. J Lipid Res. 2006 Jun;47(6):1118-1127. Pubmedid: 16582420.
  • Wang G, Deschenes RJ. Plasma membrane localization of Ras requires class C Vps proteins and functional mitochondria in Saccharomyces cerevisiae. Mol Cell Biol. 2006 Apr;26(8):3243-3255. Pubmedid: 16581797. Pmcid: PMC1446948.
  • Swarthout JT, Lobo S, Farh L, Croke MR, Greentree WK, Deschenes RJ, Linder ME. DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J Biol Chem. 2005 Sep;280(35):31141-31148. Pubmedid: 16000296.
  • Babu P, Deschenes RJ, Robinson LC. Akr1p-dependent palmitoylation of Yck2p yeast casein kinase 1 is necessary and sufficient for plasma membrane targeting. J Biol Chem. 2004 Jun;279(26):27138-27147. Pubmedid: 15105419.
  • Linder ME, Deschenes RJ. Model organisms lead the way to protein palmitoyltransferases. J Cell Sci. 2004 Feb;117(Pt 4):521-526. Pubmedid: 14730009.
  • Lu JM, Deschenes RJ, Fassler JS. Role for the Ran binding protein, Mog1p, in Saccharomyces cerevisiae SLN1-SKN7 signal transduction. Eukaryot Cell. 2004 Dec;3(6):1544-1556. Pubmedid: 15590828. Pmcid: PMC539023.
  • Dong X, Mitchell DA, Lobo S, Zhao L, Bartels DJ, Deschenes RJ. Palmitoylation and plasma membrane localization of Ras2p by a nonclassical trafficking pathway in Saccharomyces cerevisiae. Mol Cell Biol. 2003 Sep;23(18):6574-6584. Pubmedid: 12944483. Pmcid: PMC193718.
  • Lu JM, Deschenes RJ, Fassler JS. Saccharomyces cerevisiae histidine phosphotransferase Ypd1p shuttles between the nucleus and cytoplasm for SLN1-dependent phosphorylation of Ssk1p and Skn7p. Eukaryot Cell. 2003 Dec;2(6):1304-1314. Pubmedid: 14665464. Pmcid: PMC326649.
  • Linder ME, Deschenes RJ. New insights into the mechanisms of protein palmitoylation. Biochemistry-Us. 2003 Apr;42(15):4311-4320. Pubmedid: 12693927.
  • Lobo S, Greentree WK, Linder ME, Deschenes RJ. Identification of a Ras palmitoyltransferase in Saccharomyces cerevisiae. J Biol Chem. 2002 Oct;277(43):41268-41273. Pubmedid: 12193598.
  • Tao W, Malone CL, Ault AD, Deschenes RJ, Fassler JS. A cytoplasmic coiled-coil domain is required for histidine kinase activity of the yeast osmosensor, SLN1. Mol Microbiol. 2002 Jan;43(2):459-473. Pubmedid: 11985722. Pmcid: PMC2892222.
  • Li S, Dean S, Li Z, Horecka J, Deschenes RJ, Fassler JS. The eukaryotic two-component histidine kinase Sln1p regulates OCH1 via the transcription factor, Skn7p. Mol Biol Cell. 2002 Feb;13(2):412-424. Pubmedid: 11854400. Pmcid: PMC65637.
  • Zhao L, Lobo S, Dong X, Ault AD, Deschenes RJ. Erf4p and Erf2p form an endoplasmic reticulum-associated complex involved in the plasma membrane localization of yeast Ras proteins. J Biol Chem. 2002 Dec;277(51):49352-49359. Pubmedid: 12379641.
  • Ault AD, Fassler JS, Deschenes RJ. Altered phosphotransfer in an activated mutant of the Saccharomyces cerevisiae two-component osmosensor Sln1p. Eukaryot Cell. 2002 Apr;1(2):174-180. Pubmedid: 12455952. Pmcid: PMC118030.
  • Zhan XL, Hong Y, Zhu T, Mitchell AP, Deschenes RJ, Guan KL. Essential functions of protein tyrosine phosphatases PTP2 and PTP3 and RIM11 tyrosine phosphorylation in Saccharomyces cerevisiae meiosis and sporulation. Mol Biol Cell. 2000 Feb;11(2):663-676. Pubmedid: 10679022. Pmcid: PMC14801.
  • Bartels DJ, Mitchell DA, Dong X, Deschenes RJ. Erf2, a novel gene product that affects the localization and palmitoylation of Ras2 in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Oct;19(10):6775-6787. Pubmedid: 10490616. Pmcid: PMC84674.
  • Deschenes RJ, Lin H, Ault AD, Fassler JS. Antifungal properties and target evaluation of three putative bacterial histidine kinase inhibitors. Antimicrob Agents Chemother. 1999 Jul;43(7):1700-1703. Pubmedid: 10390225. Pmcid: PMC89346.
  • Tao W, Deschenes RJ, Fassler JS. Intracellular glycerol levels modulate the activity of Sln1p, a Saccharomyces cerevisiae two-component regulator. J Biol Chem. 1999 Jan;274(1):360-367. Pubmedid: 9867851. Pmcid: PMC2909977.
  • Quinby GE, Dean JP, Deschenes RJ. Expression of MFA1 and STE6 is sufficient for mating type-independent secretion of yeast a-factor, but not mating competence. Curr Genet. 1999 Feb;35(1):1-7. Pubmedid: 10022942.
  • Li S, Ault A, Malone CL, Raitt D, Dean S, Johnston LH, Deschenes RJ, Fassler JS. The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p. Embo J. 1998 Dec;17(23):6952-6962. Pubmedid: 9843501. Pmcid: PMC1171043.
  • Fassler JS, Gray WM, Malone CL, Tao W, Lin H, Deschenes RJ. Activated alleles of yeast SLN1 increase Mcm1-dependent reporter gene expression and diminish signaling through the Hog1 osmosensing pathway. J Biol Chem. 1997 May;272(20):13365-13371. Pubmedid: 9148959.
  • Quinby GE, Deschenes RJ. An amino terminal prosequence is required for efficient synthesis of S. cerevisiae a-factor. Biochim Biophys Acta. 1997 Mar;1356(1):23-34. Pubmedid: 9099988.
  • Zhan XL, Deschenes RJ, Guan KL. Differential regulation of FUS3 MAP kinase by tyrosine-specific phosphatases PTP2/PTP3 and dual-specificity phosphatase MSG5 in Saccharomyces cerevisiae. Gene Dev. 1997 Jul;11(13):1690-1702. Pubmedid: 9224718.
  • Kurth DD, Farh L, Deschenes RJ. Functional consequence of mutating conserved residues of the yeast farnesyl-protein transferase beta-subunit Ram1(Dpr1). Biochemistry-Us. 1997 Dec;36(50):15932-15939. Pubmedid: 9398327.
  • Farh L, Mitchell DA, Deschenes RJ. Farnesylation and proteolysis are sequential, but distinct steps in the CaaX box modification pathway. Arch Biochem Biophys. 1995 Apr;318(1):113-121. Pubmedid: 7726551.
  • Guan K, Farh L, Marshall TK, Deschenes RJ. Normal mitochondrial structure and genome maintenance in yeast requires the dynamin-like product of the MGM1 gene. Curr Genet. 1993 Jul;24(1-2):141-148. Pubmedid: 7916673.
  • Deschenes RJ, Resh MD, Broach JR. Acylation and prenylation of proteins. Curr Opin Cell Biol. 1990 Dec;2(6):1108-1113. Pubmedid: 2099805.
  • Fedor-Chaiken M, Deschenes RJ, Broach JR. SRV2, a gene required for RAS activation of adenylate cyclase in yeast. Cell. 1990 Apr;61(2):329-340. Pubmedid: 2158860.
  • Broach JR, Deschenes RJ. The function of ras genes in Saccharomyces cerevisiae. Adv Cancer Res. 1990;54:79-139. Pubmedid: 2153328.
  • Clarke S, Vogel JP, Deschenes RJ, Stock J. Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4643-4647. Pubmedid: 3290900. Pmcid: PMC280491.
  • Deschenes RJ, Lorenz LJ, Haun RS, Roos BA, Collier KJ, Dixon JE. Cloning and sequence analysis of a cDNA encoding rat preprocholecystokinin. Proc Natl Acad Sci U S A. 1984 Feb;81(3):726-730. Pubmedid: 6199787. Pmcid: PMC344908.
  • Marquis JK, Deschenes RJ. A reevaluation of calcium-local anesthetic antagonism. Exp Neurol. 1982 Jun;76(3):547-552. Pubmedid: 7084373.
  • Deschenes RJ, Hilt DC, Marquis JK, Mautner HG. Terbium binding to axonal membrane vesicles from lobster (Homarus americanus) peripheral nerve. A probe of calcium binding sites. Biochim Biophys Acta. 1981 Feb;641(1):166-172. Pubmedid: 7213712.
  • Deschenes RJ, Mautner HG, Marquis JK. Local anesthetics noncompetitively inhibit terbium binding to the exterior surface of nerve membrane vesicles. Biochim Biophys Acta. 1981 Dec;649(3):515-520. Pubmedid: 7317415.