Cloning and Expression Analysis of a Novel Gene, UBAP1, Possibly Involved in Ubiquitin Pathway

The 9p21-22 region shows loss of heterozygosity in up to 60% of human nasopharyngeal carcinomas (NPC), indicating the presence of a tumor suppressor gene in this region. We have identified a novel minimal common deletion region at 9p21-22. Twenty-two epithelial-derived expressed sequence tags (ESTs) in this critical region were systematically screened by differential RT-PCR to investigate the expression patterns in NPC cell line HNE1 and primary cultures of normal nasopharyngeal epithelial cells. One of these ESTs was found down-expressed in HNE1, whose differential expression was confirmed by Northern blot. Subsequently the corresponding gene sequence for this EST was established by cDNA cloning and RACE procedures (GenBank Accession No.AF222043). Furthermore, a mouse homologueof this gene was identified (GenBank Accession No.AF275549). This gene is 2.7 kb long and contains two UBA domains. It is a new member of UBA domain protein family, encoding a putative protein of 502 amino acids with a theoretical molecular mass of 55 kD, so we have named this gene UBAP1 for ubiquitin associated protein 1 (HUGO Gene Nomenclature Committee-approved symbol). Northern blot and RT-PCR analysis demonstrated a ubiquitous pattern of gene expression in human and mouse tissues. Direct sequencing analysis of the coding region of hUBAP1 following RT-PCR failed to reveal any mutations in a preliminary screening of NPC cell line HNE1 and primary nasopharyngeal carcinomas samples. However, more detailed analysis is to be performed to reveal if fine mutations of this gene are present in NPC.