Laboratory of Arthur L. Haas, PhD

Graduate Training: Northwestern University School of Medicine, 1979; Post-doctoral Training: Institute for Cancer Research
of the Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Haas Lab Photo: Art Haas, Jenny Klein, Fredrick Streich, Virginia Ronchi, Daniel Edwards, Kimberly LeCompte & Allison Wallace

Research Interests

Ubiquitin is a highly conserved 8600 dalton polypeptide distributed throughout eukaryotes. The biological effects of ubiquitin are exerted through a unique post-translational modification in which the polypeptide is covalently ligated to free amino groups on various intracellular target proteins in an ATP-coupled reaction.

The major role of ubiquitin conjugation is in targeting proteins for degradation as an essential regulatory step. Other roles for which conjugation has been implicated include gene regulation, DNA repair, stress response, cell cycle progression, various forms of muscle atrophy, and Alzheimers dementia.

We have also identified a second constitutive system within cells that is parallel but distinct from ubiquitin in which the 15 kDa interferon-like protein ISG15/UCRP is conjugated to a smaller subset of intracellular targets. ISG15 is the archetype of a small group of function-specific ubiquitin-like proteins that includes SUMO-1 and Nedd8. The conjugation of ISG15 to intracellular targets functions to regulate protein-protein interactions, in one instance acting in trans to mediate association of the target with intermediate filaments.

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Recent Publications

Ubiquitin and ubiquitin-modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU.Anderson DM, Schmalzer KM, Sato H, Casey M, Terhune SS, Haas AL, Feix JB, Frank DW.Mol Microbiol. Oct 31. (2011)

E1-E2 interactions in the ubiquitin and Nedd8 ligation pathways. Tokgöz Z, Siepmann TJ, Streich FC, Kumar B, Klein JM, Haas AL. J Biol Chem. Nov 8.(2011)

Measuring rates of ubiquitin chain formation as a functional readout of ligase activity. Ronchi, VP and Haas AL. Meth. Mol. Biol., in press.

A novel role for ATM in regulating proteasome-mediated protein degradation through suppression of the ISG15 conjugation pathway. Wood, LM, Sankar, S, Reed, RE, Haas AL, Liu, LF, McKinnon, P and Desai, SD. PloS ONE 6, e16422 (2011).

PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model. Datta R, Naura AS, Zerfaoui M, Errami Y, Oumouna M, Kim H, Ju J, Ronchi VP, Haas AL, Boulares AH. PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model. Allergy DOI: 10.1111/j.1398-9995.2011.02549.x. (2011).

Activation of ubiquitin and ubiquitin-like proteins, Streich, FC and Haas AL. Subcell. Biochem. 54, 1-16 (2010).

Ser¹²⁰ of Ubc2/Rad6 regulates ubiquitin-dependent N-end rule targeting by E3a/Ubr1. Kumar, B, LeCompte, KG, Klein, JM and Haas AL. J. Biol. Chem. 285, 41300-41309 (2010).

Regulating the regulator: Rsp5 ubiquitinates the proteasome. Haas AL. Mol Cell. 5:623-624. (2010)

Structural biology: Transformative encounters.Schulman BA, Haas AL. Nature. 463:889-890. (2010)

Hdm2 is a ubiquitin ligase of Ku70-Akt promotes cell survival by inhibiting Hdm2-dependent Ku70 destabilization. Gama V, Gomez JA, Mayo LD, Jackson MW, Danielpour D, Song K, Haas AL, Laughlin MJ, Matsuyama. S. Cell Death Differ. 16:758-769. (2009)

Cho KI, Yi H, Desai R, Hand AR, Haas AL, Ferreira PA.RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system. EMBO Rep. 10:480-486. (2009)

Haas AL. Linear polyubiquitylation: the missing link in NF-kappaB signaling. Nat Cell Biol. 11:116-118.(2009)

Giannakopoulos NV, Arutyunova E, Lai C, Lenschow DJ, Haas AL, Virgin HW. ISG15 Arg151 and the ISG15-conjugating enzyme UbE1L are important for innate immune control of Sindbis virus. J Virol. 83:1602-1610. (2009)

Haas AL. Wilkinson KD. DeTEKting ubiquitination of APC/C substrates. Cell. 133:570-572. (2008)

Haas AL. Structural insights into early events in the conjugation of ubiquitin and ubiquitin-like proteins. Mol Cell. 27:174-175. (2007)

Sorensen CM, Rempel LA, Nelson SR, Francis BR, Perry DJ, Lewis RV, Haas AL, Hansen TR. The hinge region between two ubiquitin-like domains destabilizes recombinant ISG15 in solution. Biochemistry 46:772-780. (2007)

Melner MH, Haas AL, Klein JM, Brash AR, Boeglin WE, Nagdas SK, Winfrey VP, Olson GE. Demonstration of Ubiquitin Thiolester Formation of UBE2Q2 (UBCi), a Novel Ubiquitin Conjugating Enzyme with Implantation Site-Specific Expression. Biol. Reproduction 75:395-406. (2006)

Tokgoz Z, Bohnsack RN, Haas AL. Pleiotropic effects of ATP•Mg²⁺ binding in the catalytic cycle of ubiquitin-activating enzyme. J Biol Chem. 281:14729-14737. (2006)

Haas, AL. ISG15-dependent regulation, in Protein Degradation, J. Mayer, A. Ciechanover, and R. Rechsteiner, eds., Wiley-VCH Verlag, Weinheim, Germany, 5:103-131. (2006)

Chen Y, Dai X, Haas AL, Wen R, Wang D. Proteasome-dependent down-regulation of activated Stat5A in the nucleus. Blood 108:566-574. (2006) 

Desai SD, Haas AL, Wood LM, Tsai YC, Pestka S, Rubin EH, Saleem A, Nur-E-Kamal A, Liu LF. Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. Cancer Res. 66:921-921. (2006)

Gama V, Yoshida T, Gomez JA, Basile DP, Mayo LD, Haas AL, Matsuyama S. Involvement of the ubiquitin pathway in decreasing Ku70 levels in response to drug-induced apoptosis. Exp Cell Res. 312:488-488. (2006)

Shang F, Deng G, Liu Q, Guo W, Haas AL, Crosas B, Finley D, Taylor A. Lys6-modified ubiquitin inhibits ubiquitin-dependent protein degradation. J Biol Chem. 280:20365-20365. (2005)

Narasimhan, J., Wang, M., Klein, J.M., Haas, AL*, and Kim, J.-J.P.*, Crystal structure of the interferon-induced ubiquitin-like protein ISG15. J. Biol. Chem. 280:27356-27365 (2005) (Cited by the Faculty of 1000; *corresponding authors) Reddy ST, Kumar SN, Haas AL, Dahms NM. Biochemical and functional properties of the full-length cation-dependent mannose 6-phosphate receptor expressed in Pichia pastoris. Biochem Biophys Res Commun. 309:643-651. (2003)

Kotamraju S, Tampo Y, Keszler A, Chitambar CR, Joseph J, Haas AL, Kalyanaraman B. N. Nitric oxide inhibits H2O2-induced transferrin receptor-dependent apoptosis in endothelial cells: Role of ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 100:10653-8. (2003)

Bohnsack RN, Haas AL. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer. J Biol Chem.278(29):26823-26830. (2003)

Siepmann TJ, Bohnsack RN, Tokgoz Z, Baboshina OV, Haas AL. Protein interactions within the N-end rule ubiquitin ligation pathway. J Biol Chem. 278:9448-9457. (2003)

Badciong JC, Haas AL. MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination. J Biol Chem. 277:49668-49675. (2002)

Wendelberger KJ, Burke R, Haas AL, Harenwattananon M, Simpson D. Identifying Opportunities for Vertical Integration of Biochemistry and Clinical Medicine. Adv Health Sci Educ Theory Pract. 3:157-164. (1998)

Balakirev MY, Jaquinod M, Haas AL, Chroboczek J. Deubiquitinating function of adenovirus proteinase. J Virol. 76:6323-6331. (2002)

Hamerman JA, Hayashi F, Schroeder LA, Gygi SP, Haas AL, Hampson L, CoughlinP, Aebersold R, Aderem A. Serpin 2a is induced in activated macrophages and conjugates to a ubiquitin homolog. J Immunol. 168:2415-2423. (2002)

Pru JK, Austin KJ, Haas AL, Hansen TR. Pregnancy and interferon-tau upregulate gene expression of members of the 1-8 family in the bovine uterus. Biol Reprod. 65:1471-1480. (2001)

Lawson TG, Sweep ME, Schlax PE, Bohnsack RN, Haas AL. Kinetic analysis of the conjugation of ubiquitin to picornavirus 3C proteases catalyzed by the mammalian ubiquitin-protein ligase E3alpha. J Biol Chem. 276:39629-39637. (2001)

Baboshina OV, Crinelli R, Siepmann TJ, Haas AL. N-end rule specificity within the ubiquitin/proteasome pathway is not an affinity effect. J Biol Chem. 276:39428-39437. (2001)

Macdonald JM, Haas AL, London RE. Novel mechanism of surface catalysis of protein a dduct formation. NMR studies of the acetylation of ubiquitin. J Biol Chem. 275:31908-31913. (2000)

Kurtzman AL, Gregori L, Haas AL, Schechter N. Ubiquitination and degradation of the zebrafish paired-like homeobox protein VSX-1. J Neurochem, 75:48-55. (2000)

Wilkinson KD, Laleli-Sahin E, Urbauer J, Larsen CN, Shih GH, Haas AL, Walsh ST, Wand AJ. The binding site for UCH-L3 on ubiquitin: mutagenesis and NMR studies on the complex between ubiquitin and UCH-L3. J Mol Biol. 291:1067-1077. (1999)

Potter JL, Narasimhan J, Mende-Mueller L, Haas AL. Precursor processing of pro-ISG15/UCRP, an interferon-beta-induced ubiquitin-like protein. J Biol Chem. 274:25061-25068. (1999)

Macdonald JM, LeBlanc DA, Haas AL, London RE. An NMR analysis of the reaction of ubiquitin with [acetyl-1-13C]aspirin. Biochem Pharmacol. 57:1233-1244. (1999)

Obin M, Mesco E, Gong X, Haas AL, Joseph J, Taylor A. Neurite outgrowth in PC12 cells. Distinguishing the roles of ubiquitylation andubiquitin-dependent proteolysis. J Biol Chem. 274:11789-11795. (1999)

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