HtrA serine proteases as potential therapeutic targets in cancer.
The human HtrA family of serine proteases consists of four members: HtrA1, HtrA2, HtrA3 and HtrA4. Although prokaryotic HtrA proteins are well characterized in their dual roles as chaperones and proteases that degrade misfolded proteins in the periplasm, some members of mammalian HtrA proteins are described as potential modulators of programmed cell death and chemotherapy-induced cytotoxicity. Goal of this review article is to describe the molecular alterations associated with these HtrA serine proteases and how these alterations may be associated with tumor behavior and response to chemotherapy. We will also discuss evidence that chemotherapeutic drugs regulate the expression and activation of HtrA serine proteases and that these proteases contributes to programmed cell death. Finally, we will discuss the potential role of epigenetic therapy in targeting the expression and activation of HtrA serine proteases and the mechanisms by which these proteases enhance cytotoxic effect of conventional chemotherapy.
Chien
Jeremy
J
Department Biochemistry, Sect. Pathology, Via L. Armanni, 5, 80138 Naples, Italy.
Campioni
Mara
M
Shridhar
Viji
V
Baldi
Alfonso
A
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D016503:Drug Delivery Systems; D044127:Epigenesis, Genetic; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D012697:Serine Endopeptidases