Regulation of the Expression of Heme Oxygenase-1: Signal Transduction, Gene Promoter Activation, and Beyond.

MEDINA VICTORIA; DAIANA SAPOCHNIK; MARTIN GARCIA SOLÁ; OMAR COSO

ANTIOXIDANTS & REDOX SIGNALING

MARY ANN LIEBERT INC

Lugar: New York; Año: 2020 vol. 10 p. 1033 - 1044

1523-0864

Significance: Heme oxygenase-1 (HO-1) is a ubiquitous 32-kDa protein expressed in many tissues and highlyinducible. They catalyze the degradation of the heme group and the release of free iron, carbon monoxide, andbiliverdin; the latter converted to bilirubin by biliverdin reductase. Its role in the regulation of cellular homeostasisis widely documented. Studying regulation of HO-1 expression is important not only to understandthe life of healthy cells but also the unbalances in cell metabolism that lead to disease.Recent Advances: The regulation of its enzymatic activity depends heavily upon changes in expression studiedmainly at the transcriptional level. Current knowledge regarding HO-1 gene expression focuses primarily ontranscription factors such as Nrf2 (nuclear factor erythroid 2-related factor 2), AP-1 (activator protein-1), andhypoxia-inducible factor, which collect signal transduction pathway information at the HO-1 gene promoter.AU4c Understanding of gene expression regulation is not limited to transcription factor activity but also involves anextended range of post- or cotranscriptional regulated events.Critical Issues: In addition to the regulation of gene promoter activity, alternative splicing, alternative polyadenylation,and regulation of messenger RNA stability play critical roles in changes in HO-1 gene expressionAU5c levels, involving specific factors, proteins, and microRNAs. All potential targets for diagnosis or treatment ofdiseases are related to HO-1 dysregulation.Future Directions: Unbalances in the tightly regulated gene expression mechanisms lead to cell transformationand cancer development. Knowledge of these events and signal transduction cascades triggered by oncogenes inwhich HO-1 plays a critical role is of upmost importance for research in this field.