Linda M. Hendershot, PhD

Linda M. Hendershot, PhD

Member, St. Jude Faculty

Departments

Genetics / Tumor Cell Biology

Contact Information

Linda Hendershot, PhD
Genetics / Tumor Cell Biology
MS350, Room DTRT5002
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: linda.hendershot@stjude.org
Phone: (901) 595-2475
FAX: (901) 595-2381

Education

PhD - University of Alabama, Birmingham

Research Interests

  • Control of the synthesis and assembly of secretory proteins in the ER
  • Regulation of immunoglobulin transport
  • Elucidation of ER stress-induced signal transduction pathways
  • Role of the ER stress response in regulating tumor chemosensitivity

ER chaperones

Endoplasmic reticulum

Identification and disposal of misfolded secretory pathway proteins

Protein folding in the secretory pathway and the response of cells to alterations in the ER environment during normal and pathological conditions

The cellular response to imbalances in protein folding in the ER and its role in normal cellular differentiation and disease

Laboratory


Selected Publications

Feige MJ, Hendershot LM, Buchner J. How antibodies fold. TIBS 2009 (in press).

Vembar S, Jin Y, Brodsky JL, Hendershot LM. Complementation of the Hsp40-dependent yeast phenotypes differ in their requirements for the J domain and substrate binding activities of a mammalian homolog. J Biol Chem 2009 (in press).

Ma Y, Shimizu Y, Mann MJ, Hendershot LM. Plasma cell differentiation initiates a limited ER stress response by specifically suppressing the PERK-dependent branch of the UPR. Cell Stress & Chap 2009 (in press).

Shimizu Y, Hendershot LM. Oxidative folding: cellular strategies for dealing with the resultant equimolar production of reactive oxygen species. Forum Review, Antioxidants & Redox Signaling 11;2317-2331, 2009.

Shimizu Y, Meunier L, Hendershot LM. pERp1 is dramatically upregulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin. PNAS 106:17013-17018, 2009.

Feige MJ, Groscurth S, Marcinowski M, Shimizu Y, Kessler H, Hendershot LM, Buchner J. An unfolded CH1 domain controls the assembly and secretion of lgG antibodies. Mol Cell 34:569-579, 2009.

Jin Y, Hendershot LM. ERdj3, a lumenal ER DnaJ homolog binds directly to unfolded proteins in the mammalian ER: identification of cricital residues. Biochemistry 48:41-49, 2009.

Jin Y, Awad W, Petrova K Hendershot LM. Regulated release of ERdj3 from unfolded proteins by BiP. EMBO J 27:2873-2882, 2008.

Okuda-Shimizu Y, Shen Y, Hendershot LM. Quality control in the endoplasmic reticulum. In: The Handbook of Cell Signaling. Edited by R. Bradshaw and E. Dennis, Elsevier, Inc., 2008 (in press).

Awad W, Estrada I, Shen Y, Hendershot LM. Characterization of BiP mutants that are unable to interact with resident ER DnaJ family members provides insights into inter-domain interactions in BiP. Proc Natl Acad Sci USA 105:1164-1169, 2008.

Okuda-Shimizu Y, Hendershot LM. Characterization of an ERAD pathway for non-glycosylated BiP substrates, which requires Herp. Mol Cell 28:544-554, 2007.

Shen Y, Hendershot LM. XBP-1 regulates the OBF-1/BOB-1/OCA-B transcription coactivator, which controls Ig heavy chain expression during plasma cell differentiation. J Immunol 179:2969-2978, 2007.

Richter K, Hendershot LM, Freeman BC. The cellular world according to Hsp90. Nature Structural and Molecular Biology 14:90-94, 2006.

Liao N, Hendershot LM. The unfolded protein response: contributions to development and disease. In: Cell Stress Proteins. Edited by S.K. Calderwood, Kluwer & Plenum, pp. 57-88, 2007.

Pirot P, Ortis F, Cnop M, Ma Y, Hendershot LM, Eizirik DL, Cardozo AK. Transcriptional regulation of the endoplasmic reticulum (ER) stress gene Chop in pancreatic insulin producing cells. Diabetes 56:1069-1077, 2007.

Mann MJ, Hendershot LM. UPR activation alters chemosensitivity of tumor cells. Cancer Biology and Therapy 5:736-740, 2006.

Lee AS, Hendershot LM. ER stress and cancer. Cancer Biology and Therapy 5:721-722, 2006.

Brewer JW, Hendershot LM. Building an Antibody Factory: A Job for the Unfolded Protein Response. Nature Immunology 6:23-29, 2005.

Shen Y, Chung K, Hendershot LM. Protein folding in the endoplasmic reticulum via the HSP70 family. In: Handbook of Protein Folding. Edited by J. Buchner and T. Kiefhaber, Wiley/Verlag, Vol. 4, pp. 563- 603, 2005.

Senderek J, Krieger, M, Stendel C, Herrman R, Bergmann C, Breitbach-Faller N, Esser K-J, Kruttgen A, Hendershot LM, Schröder JM, Lochmüller H, Voit T, Weis J, Ebinger F, Zerres K. Mutations in BAP/SIL1 cause Marinesco Sjogren syndrome, a cerebellar ataxia with cataract and myopathy. Nature Genetics 37:1312-1314, 2005.

Dudek J, Greiner M, Müller A, Kappl R, Hendershot LM, Kopsch K, Nastainczyk W, Zimmermann, R. ERj1p plays a basic role in protein biogenesis at the endoplasmic reticulum. Nature Structural Biology12:1008-1014, 2005.

Gray M, Mann M, Nitiss J, Hendershot LM. Activation of the UPR is necessary and sufficient for reducing topoisomerase II α protein levels and decreasing sensitivity to topoisomerase targeted drugs. Mol Pharmacology 68:1699-1707, 2005.

Alder N, Shen Y, Brodsky JL, Hendershot LM, Johnson, AE. The molecular mechanisms underlying BiP-mediated gating of the sec61 translocon. J Cell Biol 168:289-399, 2005.

Shen Y, Hendershot LM. ERdj3, a stress-inducible ER DnaJ homologue, serves as a co-factor for BiP’s interactions with unfolded substrates. Mol Biol Cell 16:40-50, 2005.

Ma Y, Hendershot LM. The role of the unfolded protein response in tumorigenesis: friend or foe? Nature Reviews Cancer 4:966-977, 2004.

Hendershot LM. BiP is a master regulator of ER function. Dean’s Lecture, Mt. Sinai Journal of Medicine 71:289-297, 2004.

Ma Y, Hendershot LM. ER chaperone functions during normal and stress conditions. J Chem Neuroanatomy 28:51-65, 2004.

Hendershot LM, Sitia R. Antibody synthesis and assembly. In: Molecular Biology of B cells. Edited by F.W. Alt, T. Honjo and M.S. Neuberger, Elsevier Science, pp. 261-273, 2004.

Tessitore A, Martin MP, Mann L, Ingrassia A, Sano R, Ma Y, Hendershot LM, d’Azzo A. Endoplasmic reticulum stress response mediates neurodegeneration in GM1-gangliosidosis. Mol Cell 15:753-766, 2004.

Ma Y, Hendershot LM. Herp is dually regulated by both the ER stress-specific branch of the UPR and a branch that is shared with other cellular stress pathways. J Biol Chem 279:13792-13799, 2004.

Ma Y, Hendershot LM. The stressful road to antibody secretion. News and Views. Nature Immunology 4:310-311, 2003.

Ma Y, Hendershot LM. Delineation of the negative feedback regulatory loop that controls protein translation during ER stress. J Biol Chem 278:34864-34873, 2003.

Meunier L, Usherwood Y-K, Chung K-T, Hendershot LM. A sub-set of chaperones and folding enzymes form multi-protein complexes in the ER to bind nascent proteins. Mol Biol Cell 13: 4456-4469, 2002.

Chung KT, Shen Y, Hendershot LM. BAP, a newly identified protein, enhances the ATPase activity of mammalian BiP by serving as a nucleotide exchange factor. J Biol Chem 277:47557-47563, 2002.

Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot LM, Neckers L. Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1a. Mol Cell Biol 22:8506-8513, 2002.

Shen J, Chen X, Hendershot LM, Prywes R. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev Cell 3:99-111, 2002 (selected for mini-review).

Ma Y, Brewer JW, Diehl JA, Hendershot LM. Two distinct stress signaling pathways converge upon the CHOP promoter during the mammalian unfolded protein response. J Mol Biol 318:1351-1365, 2002.

Shen Y, Meunier L, Hendershot LM. Identification and characterization of a novel ER DnaJ homologue, which stimulates BiP’s ATPase activity in vitro and is induced by ER stress. J Biol Chem 277:15947-15956, 2002.

Vanhove, M, Usherwood, Y-K, Hendershot LM. Unassembled Ig heavy chains do not cycle from BiP in vivo, but require light chains to trigger their release. Immunity 15:105-114, 2001.

Hendershot LM, Bulleid, NJ. Protein-specific chaperones: The role of hsp47 begins to gel. Dispatch. Curr Biol 10:R912-R915, 2000.

Hendershot LM. Giving protein traffic the green light. News and Views. Nat Cell Biol 2:E105-106, 2000.

Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. Dynamic interactions between BiP and the ER stress receptors IRE1 and PERK in the unfolded protein response. Nat Cell Biol 2:326-332, 2000.

Last update: November 2009

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