The human Hsp70B gene at the HSPA7 locus of chromosome 1 is transcribed but non-functional

Parsian, Azemat J.; Sheren, Jamie; Tao, Ting Y.; Goswami, Prabhat C.; Malyapa, Robert S.; Rheeden, Richard Van; Watson, Michael S.; Hunt, Clayton R.

doi:10.1016/s0167-4781(00)00203-7

Cited by 52 publications

(47 citation statements)

References 13 publications

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“…To date, knowledge about Hsp70BЈ is limited. Unlike Hsp72, Hsp70BЈ is strictly inducible, having no detectable basal level of expression in most cells (Leung et al 1990;Parsian et al 2000). Interestingly, homologs for the Hsp70BЈ gene (HSP6A) are not found in rodents (Parsian et al 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike Hsp72, Hsp70BЈ is strictly inducible, having no detectable basal level of expression in most cells (Leung et al 1990;Parsian et al 2000). Interestingly, homologs for the Hsp70BЈ gene (HSP6A) are not found in rodents (Parsian et al 2000). Studies of the relationship of Hsp70BЈ to other members of the human Hsp70 family may reveal the specific functional role of this protein in the identified organisms.…”

Section: Introductionmentioning

confidence: 99%

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Hsp70B′ regulation and function

et al. 2007

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Heat shock protein (Hsp) 70BЈ is a human Hsp70 chaperone that is strictly inducible, having little or no basal expression levels in most cells. Using siRNAs to knockdown Hsp70BЈ and Hsp72 in HT-29, SW-480, and CRL-1807 human colon cell lines, we have found that the two are regulated coordinately in response to stress. We also have found that proteasome inhibition is a potent activator of hsp70BЈ. Flow cytometry was used to assay hsp70BЈ promoter activity in HT-29eGFP cells in this study. Knockdown of both Hsp70BЈ and Hsp72 sensitized cells to heat stress and increasing concentrations of proteasome inhibitor. These data support the conclusion that Hsp72 is the primary Hsp70 family responder to increasing levels of proteotoxic stress, and Hsp70BЈ is a secondary responder. Interestingly ZnSO 4 induces Hsp70BЈ and not Hsp72 in CRL-1807 cells, suggesting a stressor-specific primary role for Hsp70BЈ. Both Hsp70BЈ and Hsp72 are important for maintaining viability under conditions that increase the accumulation of damaged proteins in HT-29 cells. These findings are likely to be important in pathological conditions in which Hsp70BЈ contributes to cell survival.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hsp70B′ regulation and function

et al. 2007

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“…Here, we report an analysis of Hsp70B 0 regulation. Unlike Hsp72, Hsp70B 0 is strictly inducible, having little or no basal detectable level in most cells (Leung et al, 1990;Parsian et al, 2000), whereas Hsp72 is relatively abundant even in unstressed cells. In fact, Hsp70B 0 induction has been used as a highly sensitive biomarker of cellular stress (Leung et al, 1990;Wada et al, 2005;Wang et al, 2005).…”

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confidence: 99%

“…In fact, Hsp70B 0 induction has been used as a highly sensitive biomarker of cellular stress (Leung et al, 1990;Wada et al, 2005;Wang et al, 2005). Hsp70B 0 is also interesting from an evolutionary point of view, as the Hsp70B 0 gene HSPA6 appears to have arisen after the divergence of rodents and humans (Parsian et al, 2000). Although Hsp70B 0 shares 84% sequence identity with Hsp72, differences in the substrate binding pocket and activation profiles may confer Hsp70B 0 with a distinct cellular role.…”

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Cell number‐dependent regulation of Hsp70B′ expression: Evidence of an extracellular regulator

Noonan

Place

Rasoulpour

et al. 2006

Journal Cellular Physiology

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Hsp70B 0 is a unique member of the human Hsp70 family of chaperones about which information is scarce. Unlike the major inducible Hsp72 protein, Hsp70B 0 is strictly inducible having little or no basal expression levels in most cells. We observed that Hsp70B 0 appears transiently in response to heat stress whereas Hsp72 levels persist for many days. Also, Hsp70B 0 is optimally induced when cell numbers are low, whereas Hsp72 levels are greatest at higher cell number. Hsp70B 0 promoter activation was measured by flow cytometry using an Hsp70B 0 promoter-driven GFP construct. In heat stressed cells, promoter activation is cell number independent over a broad range. However, when cell number increases beyond a certain population size, cells are less stress inducible for Hsp70B 0 and induction becomes highly cell number-dependent. Cell number differences in Hsp70 activation cannot be explained by changes in Hsf-1 DNA-binding activity or hyperphosphorylation. Cells with few or no cell matrix attachments (laminin-coated and low attachment plates, respectively) appear to be more sensitive to cell number-dependent inhibition. Medium conditioned by the low cell number (LCN) populations supports increased Hsp70B 0 promoter activation in high cell number (HCN) cultures. Likewise, medium conditioned in HCN culture conditions causes decreased activation of Hsp70B 0 promoter in LCN cultures. As HCN-conditioned medium has all the components necessary for cell growth, two possibilities for the activation of Hsp70B 0 gene expression exist: an inhibitory component that accumulates in culture medium at HCN, or an activator that accumulates at LCN.

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“…Interestingly, the human genome includes stress-inducible Hsp70B′ that is not found in the mouse and rat genomes and hence, is not present as a potential beneficial factor in animal models of neurodegenerative diseases to combat misfolded proteins (Parsian et al 2000;Chow and Brown 2007;Noonan et al 2007a). Although stress-inducible Hsp70B′ and Hsp70 share 84% sequence homology, differences in the substrate-binding pocket and activation profiles may confer Hsp70B′ with distinct cellular roles (Noonan et al 2007a;Hageman and Kampinga 2009).…”

Section: Introductionmentioning

confidence: 99%

Heteromeric complexes of heat shock protein 70 (HSP70) family members, including Hsp70B′, in differentiated human neuronal cells

Chow

Mok

Xiao

et al. 2010

Cell Stress and Chaperones

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Human neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been termed "protein misfolding disorders." Upregulation of heat shock proteins that target misfolded aggregation-prone proteins has been proposed as a potential therapeutic strategy to counter neurodegenerative disorders. The heat shock protein 70 (HSP70) family is well characterized for its cytoprotective effects against cell death and has been implicated in neuroprotection by overexpression studies. HSP70 family members exhibit sequence and structural conservation. The significance of the multiplicity of HSP70 proteins is unknown. In this study, coimmunoprecipitation was employed to determine if association of HSP70 family members occurs, including Hsp70B′ which is present in the human genome but not in mouse and rat. Heteromeric complexes of Hsp70B′, Hsp70, and Hsc70 were detected in differentiated human SH-SY5Y neuronal cells. Hsp70B′ also formed complexes with Hsp40 suggesting a common co-chaperone for HSP70 family members.

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The human Hsp70B gene at the HSPA7 locus of chromosome 1 is transcribed but non-functional

Cited by 52 publications

References 13 publications

Hsp70B′ regulation and function

Hsp70B′ regulation and function

Cell number‐dependent regulation of Hsp70B′ expression: Evidence of an extracellular regulator

Heteromeric complexes of heat shock protein 70 (HSP70) family members, including Hsp70B′, in differentiated human neuronal cells

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