Expression, function, and regulation of the testis-enriched heat shock HSPA2 gene in rodents and humans

Abstract

The HSPA2 gene is a poorly characterized member of the HSPA (HSP70) family. HSPA2 was originally described as testis-specific and expressed at the highest level in pachytene spermatocytes of rodents, the expression of which is not induced by heat shock. HSPA2 is crucial for male fertility. However, recent advances have shown that HSPA2 is expressed in various tumors and in certain types of somatic tissues. In this review, we summarize the current knowledge on the HSPA2 expression pattern, including information on transcriptional, translational, posttranslational, and epigenetic mechanisms which regulate HSPA2 expression. We also present and discuss the current views concerning the functions of the HSPA2 protein in spermatogenetic, somatic, and cancer cells. The knowledge of the properties of HSPA2, although limited, shows this protein as a unique member of the HSPA family. However, understanding whether this protein could become a relevant cancer biomarker or a therapeutically applicable target requires extensive further studies.

Fig. 1

Summary of results concerning functional analysis of the activity of the HSPA2 promoter in transgenic mice testes. The upper diagram shows the structure of the HSPA2 transcription unit. The potential sequences implicated in regulation of the HSPA2 gene expression in rodent tissues are indicated. Note that only the regulatory sequences that were subjected to functional studies are shown. T1 (−353) and T2 (−116) transcription start sites. The bottom diagram shows the promoter fragments that were fused to a reporter gene and analyzed in transgenic mice testes. Transgene expression (positive); No transgene expression (negative). Activities of constructs 1 and 4 were reported in Scieglinska et al. (2001), those of constructs 2 and 3 were described in Widlak et al. (2007a), construct 5 was evaluated in Dix et al. (1996b), and finally, construct 6 was assessed in Scieglińska et al. (2004). Numbers are coordinates of DNA fragment position in relation to A (+1) in the ATG translation start codon. DEL deletion, MUT point mutations, tk thymidine kinase promoter