Basic and Tumour Suppressor Characteristics of Wwox

In 1996 at M. Aldaz laboratory, during the study on ductal carcinoma in situ, almost 70% LOH was detected at the 16q23.3-16q24.1 region (between the D16S515 and D16S504 markers) (1). Such a high occurrence of LOH among patients with noninvasive stages of breast cancer (BC) suggested that chromosomal abnormalities in this region could be the primary changes a driving force of tumourigenesis. These findings led first to construction of a 700-kb physical map including the deleted region (2) and then to the identification of new gene spanning both the fragile site and the minimal region of homozygous deletion. Originally the gene was cloned at M. Aldaz laboratory, MD Anderson Cancer Center, Texas and named WWOX (WW domain-containing oxidoreductase) (3). The gene itself is comprised of nine exons; their length varies from 58 to 1060 bp (3). Together with eight introns WWOX is postulated to be ca. 1 Mb long, of which the last 8th intron is the longest and spans 779639 bp (4). Its main product is a 414 AA long, 46 kDa protein containing two types of domains: two WW domains (N-terminal; responsible for proteinprotein interactions) and C-terminal the short-chain dehydrogenase/reductase (SDR) exhibiting oxidoreductase activity. Several proteins interacting with WWOX through WW domains have been identified, namely p73 (5), AP-2γ(6), YAP (Yesassociated protein) (7) and ErbB-4 (7, 8). The second JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2009, 60, Suppl 1, 47–56 www.jpp.krakow.pl