The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2

Pyruvate kinase M2 (M2-PK) controls the rate-limiting step at the end of the glycolytic pathway in normal proliferating and tumor cells. Other functions of M2-PK in addition to its role in glycolysis are little understood. The aim of this study was to identify new cellular interaction partners of M2-PK in order to discover novel links between M2-PK and cellular functions. Here we show that the SUMO E3 ligase protein PIAS3 (inhibitor of activated STAT3) physically interacts with M2-PK and its isoenzyme M1-PK. Moreover, we demonstrate that endogenous SUMO-1-M2-PK conjugates exist in mammalian cells. Furthermore, we show that transient expression of PIAS3 but not the RING domain mutant PIAS3 (C299S, H301A) is consistent with nuclear localization of M2-PK and PIAS3 and M2-PK partially colocalize in the nucleus of these cells. This study suggests a link between PIAS3 and nuclear pyruvate kinase

Hepatocyte nuclear factor (HNF) 4? expression distinguishes ampullary cancer subtypes and prognosis after resection

To investigate biological differences and prognostic indicators of different ampullary cancer (AC) subtypes

Subcellular localization of the human papillomavirus 16 E7 oncoprotein in CaSki cells and its detection in cervical adenocarcinoma and adenocarcinoma in situ

E7 is the major oncoprotein of high-risk human papillomaviruses (HPV) which causes cervical cancer. To date E7 oncoproteins have not been investigated in cervical adenocarcinoma. In this study we generated a rabbit monoclonal anti-HPV-16 E7 antibody, RabMab42-3, which recognizes a conformational epitope in the E7 carboxy-terminal zinc-finger resulting in a strong increase in the sensitivity for the detection of cell-associated HPV-16 E7 protein relative to conventional polyclonal anti-HPV-16 E7 antibodies. Using RabMab42-3, we show that the subcellular localization of endogenous HPV-16 E7 oncoprotein varies during the cell cycle in cervical cancer cells. Moreover, we demonstrate for the first time that the HPV-16 E7 oncoprotein is abundantly expressed in cervical adenocarcinoma in situ and adenocarcinoma, suggesting an important role of HPV-16 E7 for the development of these tumors. Our findings suggest that the HPV-16 E7 oncoprotein could be a useful marker for the detection of cervical adenocarcinoma and their precursors