Evidence map›Paper›PMID 25073946›Full record

ArticleCell stress & chaperones2015

Basal and stress-inducible expression of HSPA6 in human keratinocytes is regulated by negative and positive promoter regions.

Vincent P Ramirez, Michael Stamatis, Anastasia Shmukler, Brian J Aneskievich

Open access · bronzeAbstract read
In one paragraph

Article in Cell stress & chaperones, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Enhancing hepatocellular carcinoma treatment: synergistic cytotoxicity and mechanistic insights of Ramucirumab and 5-Azacytidine combination therapy.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. HSPA6 and its role in cancers and other diseases.Molecular biology reports · 2022
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Vincent P RamirezGraduate Program in Pharmacology and Toxicology, Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269-3092, USA.
Michael Stamatis
Anastasia Shmukler
Brian J Aneskievich
University of Connecticut · US

Funding

Keratinocyte Nuclear Receptor CoactivatorsR01AR048660 · NIAMS · UNIVERSITY OF CONNECTICUT STORRS · PI ANESKIEVICH, BRIAN J · 2005 to 2009
$1.4M
NIAMS NIH HHS AR048660NIAMS NIH HHS R01 AR048660
6 · The paper itself

Abstract

Epidermal keratinocytes serve as the primary barrier between the body and environmental stressors. They are subjected to numerous stress events and are likely to respond with a repertoire of heat shock proteins (HSPs). HSPA6 (HSP70B') is described in other cell types with characteristically low to undetectable basal expression, but is highly stress induced. Despite this response in other cells, little is known about its control in keratinocytes. We examined endogenous human keratinocyte HSPA6 expression and localized some responsible transcription factor sites in a cloned HSPA6 3 kb promoter. Using promoter 5' truncations and deletions, negative and positive regulatory regions were found throughout the 3 kb promoter. A region between -346 and -217 bp was found to be crucial to HSPA6 basal expression and stress inducibility. Site-specific mutations and DNA-binding studies show that a previously uncharacterized AP1 site contributes to the basal expression and maximal stress induction of HSPA6. Additionally, a new heat shock element (HSE) within this region was defined. While this element mediates increased transcriptional response in thermally stressed HaCaT keratinocytes, it preferentially binds a stress-inducible factor other than heat shock factor (HSF)1 or HSF2. Intriguingly, this newly characterized HSPA6 HSE competes HSF1 binding a consensus HSE and binds both HSF1 and HSF2 from other epithelial cells. Taken together, our results demonstrate that the HSPA6 promoter contains essential negative and positive promoter regions and newly identified transcription factor targets, which are key to the basal and stress-inducible expression of HSPA6. Furthermore, these results suggest that an HSF-like factor may preferentially bind this newly identified HSPA6 HSE in HaCaT cells.

Indexed as

Promoter Regions, GeneticBase SequenceBinding SitesCell LineDNA-Binding ProteinsElectrophoretic Mobility Shift AssayGene ExpressionHeat-Shock ProteinsHeat Shock Transcription FactorsHot TemperatureHSP70 Heat-Shock ProteinsHumansKeratinocytesMolecular Sequence DataMutagenesis, Site-DirectedReal-Time Polymerase Chain ReactionDNA-Binding ProteinsHeat-Shock ProteinsHeat Shock Transcription FactorsHSF1 protein, humanHSF2 protein, humanHSP70 Heat-Shock ProteinsHSPA6 protein, humanTranscription Factors

Identifiers

PMID25073946
PMCPMC4255259
OpenAlexW2034804978

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.