Some authors have observed that in transfected cell lines overexpressing SIAH-1, the protein was localized predominantly in the cytoplasm [6, 16, 33], whilst others reported that it was also present in the nucleus [13] and particularly associated to the nuclear RG7112 manufacturer matrix [17]. It is interesting to note that regardless if SIAH-1

was expressed predominantly in cytoplasm or in the nucleus it showed the same punctuate pattern as we observed in our results. Other data showed that SIAH-1 was highly expressed in the nucleus, and that transient expression of cytoplasmic SIAH-1 resulted Selleckchem AZD1390 in a marked increase in apoptotic cells in hepatocellular carcinoma cell lines [26, 28]. In addition, inhibition of nuclear SIAH-1 expression resulted in reduced tumor viability and deregulation of several genes involved in cell cycle regulation. These observations suggested a dual role for SIAH-1 in hepatocarcinogenesis depending on its expression level and subcellular localization. High-level expression in the cytoplasm could be related to tumor cell apoptosis, whilst reduced expression and nuclear accumulation correlates

with tumor cell proliferation [26, 28]. When other tissues were analyzed we observed a less systematic selleck compound variation between normal and tumor tissues For example in normal lung tissue samples only very low levels of SIAH-1 were detected, in contrast to the paired tumoral counterparts which displayed a heterogeneous pattern with some cells expressing very high levels of SIAH-1. These data underline the need to correlate results obtained from tissues extracts with individual cell expression patterns viewed by immunochemistry. SIAH-1 has also been implicated in the cytoplasm-nuclear translocation of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a classic glycolytic

Dapagliflozin enzyme and multi-functional protein [15]. GAPDH participates in a recently described cell death cascade in which a variety of stimuli activate the nitric oxide (NO) synthases resulting in the S-nitrosylation of GAPDH. This confers upon it the ability to bind to SIAH-1, and escort it to the nucleus where SIAH is then able to degrade key cellular proteins and initiate apoptosis. Taken together these observations suggest that SIAH-1 could play a similar role in breast carcinoma than in HHC cells depending on its expression level and sub-cellular localization. Kid/KIF22 is a nuclear protein regulated by SIAH-1, whose level fluctuate in a cell cycle-dependent manner, increasing during pre-mitotic phases and greatly decreasing during mitosis [3].