The cellular DNA damage response (DDR) ensures genomic stability and protects against genotoxic stresses. Conversely, defects in the DDR contribute to genome instability, with the resulting accumulated genetic changes capable of inducing neoplastic transformation. Thus, DDR is central to both the mechanism of oncogenesis and cancer therapy. Specifically, DDR is accomplished via a complicated meshwork of evolutionary conserved proteins, including ATM, ATR, and phospho-H2AX (γH2AX). GLTSCR2 is a nucleolar protein believed to function as a tumor suppressor, although its exact molecular mechanisms have yet to be fully elucidated. As a result of our research pertaining to the role of GLTSCR2 in tumor suppression, we have determined that GLTSCR2 is involved in DDR. Under genotoxic conditions, such as cellular exposure to UV radiation or radiomimetic drugs, GLTSCR2 expression increased and later mobilized to the nucleoplasm. Moreover, GLTSCR2 knockdown attenuated both the presence of phospho-H2AX at the nuclear foci and the phosphorylation of multiple DDR proteins, including ATM, ATR, Chk2, Chk1, and H2AX. In addition, the decreased expression of GLTSCR2 sensitized cells to DNA damage, delayed DNA repair, and abolished G2/M checkpoint activation. Our observations indicate that GLTSCR2 is a key component of DDR and GLTSCR2 seems to act as a tumor suppressor by participating in optimal DDR because DNA damage is a frequent and crucial event in oncogenesis.

Since a large number of Akabane and bovine ephemeral fever (BEF) infection occurred in the southern part of Korea in 2010, recent information about seroprevalence of Akabane virus (AKAV) and bovine ephemeral fever virus (BEFV) has been required for preventing both diseases. In this study, serological assay against AKAV and BEFV using virus neutralization assay was conducted using 1,743 bovine sera collected from Namwon, Miryang, Yeongju and Uljin which located in Southern part of Korea from March to May in 2012. The overall seropositive rates for AKAV and BEFV were found to be 49.8% and 1.2%, respectively. The regional distribution of seroprevalence for AKAV ranged from 18.1% to 63.7%. Seroprevalences of AKAV were 63.7% in Miryang, 62.3% in Uljin, 50.7% in Namwon, and 18.1% in Yeongju. The seropositive rates for AKAV in southern part of Korea were higher than the annual average at the national level. On the other hand, seropositive rates of BEFV in four regions were from 0.3 to 3.1%. In detail, regional seroprevalences were 3.1% in Miryang, 2.0% in Uljin, and 1.7% in Yeongju, and 0.3% in Namwon. Even only one year after massive outbreaks, overall seropositive rates were very low, similar to the annual average at the nation level. This result indicates that many number of cattle infected with BEFV may be replaced by new born calf or cattle in farm may not be immunized with vaccines. To prevent another epidemic, a national wide warning should be issued and more aggressive control measure must be implied. Recent global warming phenomenon could lead to more vigorous activity of haematophagous vectors and it is possible that arboviral diseases such as AKAV and BEFV are increased. Therefore, continuous sero-monitoring and extensive vaccination combined with control of haematophagous vectors are important to effectively prevent and control diseases caused by AKAV and BEFV.

Objective: Hypoxia signals the release of cytochrome c from mitochondria as well as sequential activation of caspase-9 and caspase-3 in the pathway to apoptosis. In this report, we describe novel mechanisms governing the nuclear translocation of cytochrome c during hypoxia-induced apoptosis in neuroepithelioma, SK-N-MC cells. Methods: This work focuses on an investigation of the mechanism of cytochrome c translocation by means of immunocytochemistry, cell fractionation, Western blot and caspase assay. Results: Using immunocytochemistry and subcellular fractionation, we found that caspase-9 activation precedes cytochrome c release and translocation. Inhibition of caspase-9 activity blocked these responses to hypoxia. Previous studies suggest a key role for c-Jun N-terminal kinase (JNK) in apoptosis regulation and accordingly we found that JNK activation was essential for caspase-9 activation and nuclear translocation of cytochrome c. Conclusions: In this report, we describe novel mechanisms of caspase-9-dependent nuclear translocation of cytochrome c in hypoxic injury.