Targeting of Heat Shock Protein HSPA6 (HSP70B') to the Periphery of Nuclear Speckles is Disrupted by a Transcription Inhibitor Following Thermal Stress in Human Neuronal Cells

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2016 Oct 16

PMID 27743288

Citations 8

Authors

Larissa Becirovic

Ian R Brown

Affiliations

Soon will be listed here.

Abstract

Heat shock proteins (Hsps) are a set of highly conserved proteins involved in cellular repair and protective mechanisms. The intracellular localization of inducible members of the HSPA (HSP70) family can be used as an index to identify stress-sensitive sites in differentiated human neuronal cells. Following thermal stress, the little studied HSPA6 (HSP70B') was targeted to the periphery of nuclear speckles (perispeckles) that are sites of transcription factories. Triptolide, a fast-acting transcription inhibitor, knocked down levels of the large subunit of RNA polymerase II, RPB1, during the time-frame when HSPA6 associated with perispeckles. Administration of triptolide to heat shocked human neuronal SH-SY5Y cells, disrupted HSPA6 localization to perispeckles, suggesting the involvement of HSPA6 in transcriptional recovery after stress. The HSPA6 gene is present in the human genome but is not found in the genomes of the mouse and rat. Hence current animal models of neurodegenerative diseases lack a member of the HSPA family that exhibits the feature of stress-induced targeting to perispeckles.

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References

Manzo S, Zhou Z, Wang Y, Marinello J, He J, Li Y . Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res. 2012; 72(20):5363-73. DOI: 10.1158/0008-5472.CAN-12-1006. View

Raska I, Shaw P, Cmarko D . New insights into nucleolar architecture and activity. Int Rev Cytol. 2006; 255:177-235. DOI: 10.1016/S0074-7696(06)55004-1. View

Noonan E, Fournier G, Hightower L . Surface expression of Hsp70B' in response to proteasome inhibition in human colon cells. Cell Stress Chaperones. 2008; 13(1):105-10. PMC: 2666210. DOI: 10.1007/s12192-007-0003-3. View

Soto C, Estrada L . Protein misfolding and neurodegeneration. Arch Neurol. 2008; 65(2):184-9. DOI: 10.1001/archneurol.2007.56. View

Khalouei S, Chow A, Brown I . Localization of heat shock protein HSPA6 (HSP70B') to sites of transcription in cultured differentiated human neuronal cells following thermal stress. J Neurochem. 2014; 131(6):743-54. DOI: 10.1111/jnc.12970. View

Pardue M, Ballinger D, Hogan N . The heat shock response. Cells coping with transient stress. Ann N Y Acad Sci. 1992; 663:125-38. DOI: 10.1111/j.1749-6632.1992.tb38656.x. View

Parag H, Raboy B, KULKA R . Effect of heat shock on protein degradation in mammalian cells: involvement of the ubiquitin system. EMBO J. 1987; 6(1):55-61. PMC: 553356. DOI: 10.1002/j.1460-2075.1987.tb04718.x. View

Georgopoulos C, Welch W . Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol. 1993; 9:601-34. DOI: 10.1146/annurev.cb.09.110193.003125. View

Rieder D, Trajanoski Z, McNally J . Transcription factories. Front Genet. 2012; 3:221. PMC: 3478587. DOI: 10.3389/fgene.2012.00221. View

10.

Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Cena V . Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem. 2000; 75(3):991-1003. DOI: 10.1046/j.1471-4159.2000.0750991.x. View

11.

Maden M . Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci. 2007; 8(10):755-65. DOI: 10.1038/nrn2212. View

12.

Zhang L, Yu H, Zhao X, Lin X, Tan C, Cao G . Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Neurochem Int. 2010; 57(5):547-55. DOI: 10.1016/j.neuint.2010.06.021. View

13.

Noonan E, Place R, Rasoulpour R, Giardina C, Hightower L . Cell number-dependent regulation of Hsp70B' expression: evidence of an extracellular regulator. J Cell Physiol. 2006; 210(1):201-11. DOI: 10.1002/jcp.20875. View

14.

OBrien T, Bult C, Cremer C, Grunze M, Knowles B, Langowski J . Genome function and nuclear architecture: from gene expression to nanoscience. Genome Res. 2003; 13(6A):1029-41. DOI: 10.1101/gr.946403. View

15.

Presgraves S, Ahmed T, Borwege S, Joyce J . Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. Neurotox Res. 2004; 5(8):579-98. DOI: 10.1007/BF03033178. View

16.

Lindquist S, Craig E . The heat-shock proteins. Annu Rev Genet. 1988; 22:631-77. DOI: 10.1146/annurev.ge.22.120188.003215. View

17.

Fraser P, Bickmore W . Nuclear organization of the genome and the potential for gene regulation. Nature. 2007; 447(7143):413-7. DOI: 10.1038/nature05916. View

18.

Lopez-Carballo G, Moreno L, Masia S, Perez P, Barettino D . Activation of the phosphatidylinositol 3-kinase/Akt signaling pathway by retinoic acid is required for neural differentiation of SH-SY5Y human neuroblastoma cells. J Biol Chem. 2002; 277(28):25297-304. DOI: 10.1074/jbc.M201869200. View

19.

Jonkers I, Kwak H, Lis J . Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons. Elife. 2014; 3:e02407. PMC: 4001325. DOI: 10.7554/eLife.02407. View

20.

Shorbagi S, Brown I . Dynamics of the association of heat shock protein HSPA6 (Hsp70B') and HSPA1A (Hsp70-1) with stress-sensitive cytoplasmic and nuclear structures in differentiated human neuronal cells. Cell Stress Chaperones. 2016; 21(6):993-1003. PMC: 5083669. DOI: 10.1007/s12192-016-0724-2. View