HAX‐1: A family of apoptotic regulators in health and disease

Abstract

HAX-1 comprises a family of ubiquitously expressed proteins that play important roles in the regulation of programmed cell death. Herein, we provide a comprehensive review of the expression profile of HAX-1 and its functional implications during health and disease, highlighting its direct involvement in the development of congenital neutropenia and neural abnormalities, when absent, and its contribution to the progression of psoriasis and cancer, when overexpressed. Moreover, we provide new information on the differential expression of the HAX-1 subfamily in three distinct types of epithelial cancers, including breast, skin, and colon. Our results demonstrate a significant up-regulation of the anti-apoptotic HAX-1 variant 001 in skin and colon, but not in breast and cancer cells, indicating tissue-specific differences in its expression pattern and properties during cancer formation and progression. Our findings further reveal a considerable down-regulation, if not abrogation, of three distinct, yet to be characterized, HAX-1 isoforms in breast cancer cells, suggesting that they may function in an opposite manner to the anti-apoptotic variant 001. This study aims to summarize our current knowledge on the physiological implications of the expression profile of the HAX-1 subfamily in health and disease, and provide new information on the differential expression and activities of HAX-1 members in three distinct types of cancer.

Cellular Protein HAX1 Interacts with the Influenza A Virus PA Polymerase Subunit and Impedes Its Nuclear Translocation

“…2). HAX1 is an antiapoptotic protein which is primarily located in the mitochondria, endoplasmic reticulum, and, to a lesser extent, the cytoplasm (76). It is possible that PA, through interacting with HAX1, affects the antiapoptotic function of HAX1.…”

Competition through Dimerization between Antiapoptotic and Proapoptotic HS-1-associated Protein X-1 (Hax-1)

“…Hax-1 v1 is a ubiquitously expressed protein with established antiapoptotic activity that has been studied extensively in humans and rodents (4,19). Contrary to the mouse gene, the human and rat HAX-1 genes are heavily spliced, giving rise to at least seven distinct variants that primarily differ in the NH 2 terminus (1).…”

“…Western Blotting-Immunoblot analyses were performed as described previously (19). The only modification to this protocol was that 25 mg of heart tissue was homogenized in Nonidet P-40 buffer containing 10 mM NaPO 4 , 2 mM EDTA, 10 mM NaN 3 , 0.9% NaCl, and 2% Nonidet P-40 in the presence of a protease inhibitor mixture (Roche, catalog no.…”

“…This is complicated by the presence of multiple, functionally diverse Hax-1 binding partners and the existence of many structurally distinct Hax-1 splice variants (4,19). In this study, we examined the expression profile of Hax-1 variants in healthy and stressed hearts and studied their role in modulating cell fate following insult.…”

A Direct Interaction Between Mitochondrial Proteins and Amyloid-β Peptide and its Significance for the Progression and Treatment of Alzheimer’s Disease

“…At the subcellular level, HAX-1 is predominantly localized in the mitochondria, and to a lesser extent in the ER and nuclear membrane [271,272]. In a yeast two-hybrid screen HAX-1 was identified as a binding partner of Aβ [209], however, there is no other evidence currently available connecting HAX-1 with AD or Aβ pathophysiology.…”