In addition, it is also likely that AZIN2 may affect the degradation of antizyme-targeted proteins different to ODC, since the involvement of AZ1 in the degradation of cell cycle related proteins has been reported. Although this later claim has been recently questioned, it does not rule out the possibility that AZIN2, either directly or by acting on antizymes, could regulate proteins implicated in secretory processes. In this novel scenario, AZIN2 would affect cellular processes through its action on target proteins in addition to modulate intracellular polyamine pools. Independently of the mechanisms by which AZIN2 may affect the endocrine activity of pancreas and adrenal glands, our mouse model constitutes an interesting experimental tool to explore in depth the relevance of AZIN2 in different PI-103 aspects of mouse physiology, including reproductive, neuronal and hormonal functions. Merkel cell carcinoma is an aggressive nonmelanoma skin cancer. Current therapies for MCC include surgical excision combined with radiation treatment. However, the prognosis for patients with MCC is relatively poor, with a 2-year survival of 11% at stage IV, a 5-year survival of 52% at stage III, and a 5-year survival of 67-81% at stages II-I ; 25-30% of patients will already present with distal metastasis or lymph node abnormalities at the time of diagnosis. Recent increases in MCC incidence and association with immunocompromised conditions prompted a search for an underlying viral cause. A novel human polyomavirus was discovered in MCC using digital transcriptome subtraction, a computationallydirected search for viral transcript sequences expressed in tumor tissues. Merkel cell polyomavirus has since been detected in ~80% of MCCs by multiple groups worldwide. MCV is found clonally integrated in MCC tumor cells, indicating that infection occurs prior to carcinogenesis. Two viral proteins, MCV large tumor antigen and small tumor antigen, contribute to MCC oncogenesis. Knockdown of both LT and sT results in cell death of MCVpositive MCC cell lines, as well as tumor regression in MCV-positive MCC xenografts. Knockdown of sT alone results in growth arrest of MCC cell lines. In all tumors examined to date, MCV LT is truncated by mutations that disrupt the LT helicase domain and render the virus replication incompetent. The C-terminus of LT has recently been associated with anti-proliferative properties, which may provide a TWS119 selective pressure to disrupt this region of LT during tumor initiation. Tumor-derived LT proteins, however, maintain a functional and conserved retinoblastoma protein binding motif. DTS analysis revealed that cellular genes are differentially expressed in MCV-positive MCCs, relative to MCV-negative MCCs. mRNAs for the cellular oncoprotein survivin were found to be seven-fold higher in virus positive, compared to virus negative MCC tumors.