Disease relevance of CST8

• The structure explains why substitutions of the 3' loop nucleotides have little impact on conformation of the critical 5' loop bases and accounts for wide variation in the sequences of cres from different enteroviruses and rhinoviruses [1].
• These cres form stem-loop structures sharing a common loop motif, and the HRV-14 cre can substitute functionally for the poliovirus cre in both uridylylation in vitro and RNA replication in vivo [2].
• End-stage renal failure (ESRF) developed in 11 of 18 patients in groups DIF and CRES combined, and in two of 22 patients in group MEM [3].
• For a characterization of the clinical course of crescentic glomerulonephritis (Cres. GN), reciprocals of serum creatinine concentration (1/Cr) as a function of time were studied in 24 patients [4].
• To establish efficient induction of Cre mediated DNA recombination in primary cells, mouse embryonic fibroblast, keratinocyte, and primary preosteoblast, we tested various recombinant Cres by fusing of protein transduction domain in human immunodeficiency virus (HIV) transactivator of transcription (TAT-PTD) to the N- and/or C-terminus [5].

High impact information on CST8

• Internally located, cis-acting RNA replication elements, termed cres, are essential for replication of the genomes of picornaviruses such as human rhinovirus 14 (HRV-14) and poliovirus because they template uridylylation of the protein primer, VPg, by the polymerase 3D(pol) [2].
• Furthermore, chromosomal mapping studies show that the Cres gene co-segregates with the cystatin C gene on mouse chromosome 2 [6].
• Our earlier studies in mouse have shown that the cystatin-related epididymal spermatogenic (CRES) protein is highly expressed in elongating spermatids in the testis and is present in mouse sperm acrosomes, suggesting specific roles in sperm function, fertilization, or both [7].
• Furthermore, reverse transcription-polymerase chain reaction detected CRES mRNA in the epididymis [7].
• Therefore, the present study was undertaken to characterize the human ortholog of mouse CRES: Northern blot and in situ hybridization experiments showed that CRES is highly expressed in the human testis, specifically within clusters of round spermatids [7].

Biological context of CST8

• In this report, studies were carried out to examine CRES gene expression in the testis as well as to characterize the CRES protein in the testis and epididymis [8].
• In situ hybridization experiments revealed that within the testis CRES gene expression is stage-specific during spermatogenesis and is exclusively expressed by the round spermatids of Stages VII-VIII and the early elongating spermatids of Stages IX and X [8].
• Transient appearance of CRES protein during spermatogenesis and caput epididymal sperm maturation [8].
• Finally, to test the in vivo function of the C/EBP sites in cres gene expression, transfection studies were performed in L beta T2 gonadotroph cells and two heterologous cell systems [9].
• Two putative CCAAT/enhancer binding protein (C/EBP) transcription factor binding motifs exist within the first 135 base pairs of cres promoter [9].

Anatomical context of CST8

• However, whether the human CRES gene is similar to that of the mouse and is expressed in germ cells has not yet been determined [7].
• However, in contrast to the acrosomal localization of CRES protein in mouse spermatozoa, indirect immunofluorescence of human spermatozoa treated with methanol/acetic acid using anti-human CRES antibodies revealed that CRES was strictly localized to the equatorial segment [7].
• To determine whether CRES was associated with the plasma membrane, live spermatozoa were incubated with CRES antibody after capacitation and acrosome reaction [7].
• The expression of this gene, termed CRES (cystatin-related epididymal and spermatogenic), was shown to be highly restricted to the proximal caput epididymal epithelium with less expression in the testis and no expression in the 24 other tissues examined [8].

Associations of CST8 with chemical compounds

• The CRES protein is a member of the cystatin superfamily of cysteine protease inhibitors with restricted expression in stage-specific germ cells, proximal caput epididymidis, and anterior pituitary gonadotroph cells [9].
• Groups DIF and CRES received intensive treatment with high-dose prednisone and cytotoxic drugs [3].
• A simple and sensitive HPLC method for the determination of phenolic compounds, i.e., phenol (Phe), cresols (Cres) and xylenols (Xyls), was developed [10].

Analytical, diagnostic and therapeutic context of CST8

• Western blot analysis of testicular and epididymal proteins showed that the CRES antibody specifically recognized a predominant 19 kDa CRES protein and a less abundant 14 kDa form [8].

References