Expression of various types of alternatively spliced WAPL transcripts in human cervical epithelia

Abstract

We have previously identified a novel gene WAPL that is inducible by human papillomavirus (HPV) E6 and E7 oncoproteins, and is associated with uterine cervical carcinogenesis. A WAPL splice variant named Friend of EBNA2 (FOE) has also been characterized as a binding partner of the Epstein-Barr virus transformation-related protein EBNA2. On the other hand, recent studies have revealed that WAPL is a cohesin-binding protein and promotes sister-chromatid resolution in mitotic prophase. These data demonstrate that WAPL plays an important role in tumorigenesis and cell cycle progression. In this study, we have isolated a large number of additional alternatively spliced WAPL variants from various cervical epithelia. Each variant consists of a variable 5'-terminal region and the conserved remainder. In addition, we have confirmed the genomic organization of the 5'-region of the WAPL gene, and have investigated the characteristic features of the WAPL variants and their products. Furthermore, we have determined the HPV types of the expressed E6/E7 transcripts in the cervical epithelia with a novel PCR protocol. These results should shed light on a novel aspect of WAPL function.