The Role of Hax-1 in Neuronal Death

Review Article

Austin J Pharmacol Ther. 2014; 2 (9).1051

The Role of Hax-1 in Neuronal Death

Jing Hu and Jiukuan Hao*

Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, USA

*Corresponding author: : JiukuanHao, Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA

Received: August 02, 2014; Accepted: October 06, 2014; Published: October 07, 2014


HS-1 associated protein X-1 (Hax-1), an intracellular protein, with molecular weight of 35-kDa is encoded by the Hax-1 gene. It was first discovered as a binding partner of hematopoietic cell-specific protein 1 (HS-1), a protein involved in the maturation of T cells, which indicates involvement of Hax-1 in immune response. In addition to its involvement in immune response, Hax-1 is recently found to be involved in cell apoptosis. Hax-1 interacts with a number of intracellular substances including caspase-3, caspase-9 and the mitochondrial proteases to inhibit apoptosis and promote cell survival and proliferation. It has been found that Hax-1 plays an important role in the development of the central nervous systemand the pathophysiology of some neurological diseases. Thus, this molecule may represent a new target for therapy of some neurological diseases with Hax-1 dysfunction. However, themechanism of action of Hax-1 in these processes remains unclear. This review aims to summarize the current knowledge regarding therole of Hax-1 in neuronal death.

Keywords: Hax-1; Ischemia; Apoptosis; Caspase; Traumatic brain injury; Epilepticus


Hax-1was firstly identified in B cell signal transduction by a yeast two-hybrid assay [1-3]. The prototypical Hax-1 is a 35KDa protein, but its size varies from ~26 to ~35KDa due to alternative splicing patterns of the Hax-1 gene [1,4]. Hax-1 protein contains two putative Bcl-2 homology (BH1 and BH2) domains, a PEST motif (proline, glutamic acid, serine, threonine), and a COOH-terminal transmembrane (TM) domain, which contains several protein-binding regions. The NH2-terminal of Hax-1 has an acid box (amino acids 30–41) with unknown function, composed mostly of glutamic and aspartic acids [4]. The putative PEST sequence of Hax-1 (amino acids 104–117) suggests its rapidly degradation (Figure 1). Due to its homology and structural similarities to the Bcl-2, it was thought as a novel protein that regulates apoptosis and promotes cell survival [5,6]. The Hax-1 is mainly localized in mitochondria, the endoplasmatic reticulum and the nuclear envelope [3], which indicates different functions of Hax- 1. The studies have found that Hax-1 interacts with various proteins to regulate cell apoptosis [7,8], Ca2+ homeostasis [5,9], cell mobility, migration [10,11], transcript stability and transport [12-14]. Although Hax-1 plays key roles in a various of cellular functions mentioned above, in this review, we focus on the anti-apoptotic property of Hax- 1 and its involvement in neuronal degeneration and apoptosis.

Citation: Hu J and Hao J. The Role of Hax-1 in Neuronal Death. Austin J Pharmacol Ther. 2014; 2 (9).1051. ISSN: 2373-6208.