scholarly journals Partners in Mischief: Functional Networks of Heat Shock Proteins of Plasmodium falciparum and Their Influence on Parasite Virulence

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 295 ◽  
Author(s):  
Michael O. Daniyan ◽  
Jude M. Przyborski ◽  
Addmore Shonhai
Keyword(s):  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Quality ◽  
A Genome ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Human Proteins ◽  
Protein Quality Control System ◽  
Shock Proteins

The survival of the human malaria parasite Plasmodium falciparum under the physiologically distinct environments associated with their development in the cold-blooded invertebrate mosquito vectors and the warm-blooded vertebrate human host requires a genome that caters to adaptability. To this end, a robust stress response system coupled to an efficient protein quality control system are essential features of the parasite. Heat shock proteins constitute the main molecular chaperone system of the cell, accounting for approximately two percent of the malaria genome. Some heat shock proteins of parasites constitute a large part (5%) of the ‘exportome’ (parasite proteins that are exported to the infected host erythrocyte) that modify the host cell, promoting its cyto-adherence. In light of their importance in protein folding and refolding, and thus the survival of the parasite, heat shock proteins of P. falciparum have been a major subject of study. Emerging evidence points to their role not only being cyto-protection of the parasite, as they are also implicated in regulating parasite virulence. In undertaking their roles, heat shock proteins operate in networks that involve not only partners of parasite origin, but also potentially functionally associate with human proteins to facilitate parasite survival and pathogenicity. This review seeks to highlight these interplays and their roles in parasite pathogenicity. We further discuss the prospects of targeting the parasite heat shock protein network towards the developments of alternative antimalarial chemotherapies.

scholarly journals Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 21 ◽  
Author(s):  
Gaëtan Jego ◽  
François Hermetet ◽  
François Girodon ◽  
Carmen Garrido
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Fate ◽  
Protein Quality ◽  
Immune Cell ◽  
Therapeutic Option ◽  
Specific Cell ◽  
Shock Proteins ◽  
Multicellular Organisms ◽  
Stat5 Transcription Factor

While cells from multicellular organisms are dependent upon exogenous signals for their survival, growth, and proliferation, commitment to a specific cell fate requires the correct folding and maturation of proteins, as well as the degradation of misfolded or aggregated proteins within the cell. This general control of protein quality involves the expression and the activity of molecular chaperones such as heat shock proteins (HSPs). HSPs, through their interaction with the STAT3/STAT5 transcription factor pathway, can be crucial both for the tumorigenic properties of cancer cells (cell proliferation, survival) and for the microenvironmental immune cell compartment (differentiation, activation, cytokine secretion) that contributes to immunosuppression, which, in turn, potentially promotes tumor progression. Understanding the contribution of chaperones such as HSP27, HSP70, HSP90, and HSP110 to the STAT3/5 signaling pathway has raised the possibility of targeting such HSPs to specifically restrain STAT3/5 oncogenic functions. In this review, we present how HSPs control STAT3 and STAT5 activation, and vice versa, how the STAT signaling pathways modulate HSP expression. We also discuss whether targeting HSPs is a valid therapeutic option and which HSP would be the best candidate for such a strategy.

scholarly journals Alzheimer Cells on Their Way to Derailment Show Selective Changes in Protein Quality Control Network

2020 ◽  
Vol 7 ◽  
Author(s):  
Margreet B. Koopman ◽  
Stefan G. D. Rüdiger
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Quality Control ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Brain Regions ◽  
Control Network ◽  
Shock Proteins

Alzheimer’s Disease is driven by protein aggregation and is characterized by accumulation of Tau protein into neurofibrillary tangles. In healthy neurons the cellular protein quality control is successfully in charge of protein folding, which raises the question to which extent this control is disturbed in disease. Here, we describe that brain cells in Alzheimer’s Disease show very specific derailment of the protein quality control network. We performed a meta-analysis on the Alzheimer’s Disease Proteome database, which provides a quantitative assessment of disease-related proteome changes in six brain regions in comparison to age-matched controls. We noted that levels of all paralogs of the conserved Hsp90 chaperone family are reduced, while most other chaperones – or their regulatory co-chaperones - do not change in disease. The notable exception is a select group consisting of the stress inducible HSP70, its nucleotide exchange factor BAG3 – which links the Hsp70 system to autophagy - and neuronal small heat shock proteins, which are upregulated in disease. They are all members of a cascade controlled in the stress response, channeling proteins towards a pathway of chaperone assisted selective autophagy. Together, our analysis reveals that in an Alzheimer’s brain, with exception of Hsp90, the players of the protein quality control are still present in full strength, even in brain regions most severely affected in disease. The specific upregulation of small heat shock proteins and HSP70:BAG3, ubiquitous in all brain areas analyzed, may represent a last, unsuccessful attempt to advert cell death.

The primary structure of a Plasmodium falciparum polypeptide related to heat shock proteins

1987 ◽  
Vol 26 (1-2) ◽  
pp. 61-67 ◽  
Author(s):  
Yong-Fan Yang ◽  
Peerapan Tan-ariya ◽  
Yagya D. Sharma ◽  
Araxie Kilejian
Keyword(s):  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Primary Structure ◽  
Shock Proteins

Heat Shock Factor (HSF): The Promoter of Chaperone Genes. A Mini Review

2018 ◽  
Vol 16 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Natália Galdi Quel ◽  
Carlos H.I. Ramos
Keyword(s):  
Heat Shock ◽  
Molecular Chaperones ◽  
Protein Quality ◽  
Cell Function ◽  
Heat Shock Factor ◽  
Protein Homeostasis ◽  
General Knowledge ◽  
Protein Quality Control System ◽  
Shock Proteins ◽  
And Function

Protein homeostasis, or proteostasis, is required for proper cell function and thus must be under tight maintenance in all circumstances. In crowded cell conditions, protein folding is sometimes unfavorable, and this condition is worsened during stress situations. Cells cope with such stress through the use of a Protein Quality Control system, which uses molecular chaperones and heat shock proteins as its major players. This system aids with folding, avoiding misfolding and/or reversing aggregation. A pivotal regulator of the response to heat stress is Heat Shock Factor, which is recruited to the promoters of the chaperone genes, inducting their expression. This mini review aims to cover our general knowledge on the structure and function of this factor.

Two major phosphoproteins of Plasmodium falciparum are heat shock proteins

1993 ◽  
Vol 59 (1) ◽  
pp. 83-94 ◽  
Author(s):  
Barbara Kappes ◽  
Bernd W. Suetterlin ◽  
Renate Hofer-Warbinek ◽  
Rok Humar ◽  
Richard M. Franklin
Keyword(s):  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Shock Proteins

scholarly journals α-Crystallin-Type Heat Shock Proteins: Socializing Minichaperones in the Context of a Multichaperone Network

2002 ◽  
Vol 66 (1) ◽  
pp. 64-93 ◽  
Author(s):  
Franz Narberhaus
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Quality ◽  
Chaperone Activity ◽  
Close Cooperation ◽  
Irreversible Aggregation ◽  
Functional Features ◽  
Shock Proteins ◽  
And Function ◽  
Temperature Upshift

SUMMARY α-Crystallins were originally recognized as proteins contributing to the transparency of the mammalian eye lens. Subsequently, they have been found in many, but not all, members of the Archaea, Bacteria, and Eucarya. Most members of the diverse α-crystallin family have four common structural and functional features: (i) a small monomeric molecular mass between 12 and 43 kDa; (ii) the formation of large oligomeric complexes; (iii) the presence of a moderately conserved central region, the so-called α-crystallin domain; and (iv) molecular chaperone activity. Since α-crystallins are induced by a temperature upshift in many organisms, they are often referred to as small heat shock proteins (sHsps) or, more accurately, α-Hsps. α-Crystallins are integrated into a highly flexible and synergistic multichaperone network evolved to secure protein quality control in the cell. Their chaperone activity is limited to the binding of unfolding intermediates in order to protect them from irreversible aggregation. Productive release and refolding of captured proteins into the native state requires close cooperation with other cellular chaperones. In addition, α-Hsps seem to play an important role in membrane stabilization. The review compiles information on the abundance, sequence conservation, regulation, structure, and function of α-Hsps with an emphasis on the microbial members of this chaperone family.

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