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Human papillomavirus (HPV) is considered to be a necessary but not sufficient cause for cervical cancer. The host immunogenetic background plays an important role in the persistence of HPV infection and subsequent development of cervical cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed mainly on activated T cells and is important in the down-regulation of T-cell activation. The aim of this study was to determine if polymorphisms of the CTLA-4 gene are associated with HPV-induced cervical cancer in Taiwanese women. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype -318 C/T, +49 A/G and CT60 A/G polymorphisms in 144 women with cervical squamous cell carcinoma (CSCC) and 378 ethnicity-matched healthy control women. The presence and genotypes of HPV in CSCC were determined by E6-, E7-based nested polymerase chain reaction. The frequency of C/T genotype of -318 C/T polymorphism was significantly higher in patients with HPV-16-positive CSCC compared with controls (odds ratio = 1.99, 95% confidence interval = 1.16-3.42, P(c) = 0.03). No significant associations were found for +49 A/G and CT60 A/G polymorphisms. Analysis of haplotypes, computationally inferred from genotype data, also revealed no significant differences in distribution among all subjects with CSCC, those with HPV-16-positive CSCC and controls. Our results suggest that the -318 C/T variant in the promoter region of the CTLA-4 gene is associated with HPV-16-associated CSCC in Taiwanese women.

Objective To explore, using 4D ultrasound, the importance of location and tension of transobturator suburethral tape (TOT) with respect to surgical outcome. Methods

The SUMO proteins are a class of small ubiquitin-like modifiers. SUMO is attached to a specific lysine side chain on the target protein via an isopeptide bond with its C-terminal glycine. There are at least four SUMO proteins in humans, which are involved in protein trafficking and targeting. A truncated human SUMO-2 protein that contains residues 9-93 was expressed in Escherichia coli and crystallized in two different unit cells, with dimensions of a ¼ b ¼ 75.25 Å , c ¼ 29.17 Å and a ¼ b ¼ 74.96 Å , c ¼ 33.23 Å , both belonging to the rhombohedral space group R3. They diffracted X-rays to 1.6 Å and 1.2 Å resolution, respectively. The structures were determined by molecular replacement using the yeast SMT3 protein as a search model. Subsequent refinements yielded R/R free values of 0.169/0.190 and 0.119/ 0.185, at 1.6 Å and 1.2 Å , respectively. The peptide folding of SUMO-2 consists of a half-open b-barrel and two flanking a-helices with secondary structural elements arranged as bbabbab in the sequence, identical to those of ubiquitin, SMT3 and SUMO-1. Comparison of SUMO-2 with SUMO-1 showed a surface region near the C terminus with significantly different charge distributions. This may explain their distinct intracellular locations. In addition, crystalpacking analysis suggests a possible trimeric assembly of the SUMO-2 protein, of which the biological significance remains to be determined.Keywords: homology modeling; molecular interactions; protein modification; surface charge distributions; synchrotron radiations.Control of protein expression and regulation of protein activities are central to the cellular processes in an organism. Many proteins are rather short lived, and are eventually targeted to proteosomes for degradation via conjugation with ubiquitin [1]. However, the functions of various proteins are not only a matter of time but also a matter of place. Thus, newly synthesized proteins must be directed toward specific subcellular compartments. SUMO is the acronym for small ubiquitin-like modifier and named after its three-dimensional structural similarity to ubiquitin. Both SUMO and ubiquitin are attached to target proteins by forming an isopeptide bond between the C-terminal glycine and a specific lysine side chain on the target [2]. The extra amino acids beyond the last glycine-glycine motif of native SUMO proteins are proteolytically removed in vivo. In mammals, there are at least four different SUMO proteins, SUMO-1, -2, -3 and -4. The human hSMT3 cDNA encoding the SUMO-2 protein was first reported by Mannen et al. [3]. SUMO-2 and SUMO-3 share 87% sequence identity with each other, but they have only 47% identity with SUMO-1 [4]. The novel SUMO-4 associated with diabetes is also more similar in sequence to SUMO-2 than to SUMO-1 [5].The first three-dimensional structure of SUMO-1 determined by NMR showed that the SUMO proteins are remarkably similar in protein fold to ubiquitin despite the amino acid sequence identity of only 18% [6]. Recently, a high-resolution NMR structure of SUMO-1 was determi...

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