Heat-shock induced protein modifications and modulation of enzyme activities.
Upon heat stress, the cell physiology is profoundly altered. The extent of the alterations depends on the severity of the stress and may lead to cell death. The heat shock response is an array of metabolic changes characterized by the impairment of major cellular functions and by an adaptative reprogramming of the cell metabolism. The enhanced synthesis of the HSPs is a spectacular manifestation of this reprogramming. Numerous post translational modifications of proteins occur in response to heat stress and can be related to altered cellular functions. Some proteins are heat-denatured and temporarily inactivated. Heat-denaturation is reversible, chaperones may contribute to the repair. The extent of heat-denaturation depends on the cell metabolism: (a) it is attenuated in thermotolerant cells or in cells overexpressing the appropriate chaperones (b) it is enhanced in energy-deprived cells. Covalent modifications may also rapidly alter protein function. Changes in protein glycosylation, methylation, acetylation, farnesylation, ubiquitination have been found to occur during stress. But protein phosphorylation is the most studied modification. Several protein kinase cascades are activated, among which the various mitogen activated protein kinase (MAP kinase) cascades which are also triggered by a wide range of stimuli. As a possible consequence, stress modifies the phosphorylation status and the activity of components from the transcriptional and translational apparatuses. The same kinases also target key enzymes of the cellular metabolism. Protein denaturation results in constitutive hsp titration, this titration is a signal to trigger the heat-shock gene transcription and to activate some of the protein kinase cascades.
Bensaude
O
O
Génétique Moléculaire, Ecole Normale Supérieure, Paris, France.
Bellier
S
S
Dubois
M F
MF
Giannoni
F
F
Nguyen
V T
VT
D000818:Animals; D006031:Glycosylation; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D010766:Phosphorylation; D011487:Protein Conformation; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013312:Stress, Physiological
D006360:Heat-Shock Proteins; D011506:Proteins