The inhibitors of apoptosis proteins (IAPs) are a widely expressed gene family of apoptotic inhibitors. The central mechanisms of IAP apoptotic suppression appear to be through direct caspases and pro-caspase inhibition. Recently, a new human gene encoding a structurally and unique IAP designated Survivin has been identified. Survivin (human 142 aa, ~16.5 kDa, chromosome 17q25; Mouse TIAP/Survivin 140 aa) contains a single baculovirus IAP repeat and lacks a C-terminal RING finger. It has the property of oncofetal antigens: highly expressed in less-differentiated embryonic cells or rapidly dividing tumor cell but not in fully differentiated adult tissues. Elevated levels of Survivin are found in human fetal lung, liver, heart, kidney, and gastrointestinal tract. In mouse embryonic tissues, Survivin is detected in most tissues. High level of Survivin was found in most common human cancer, including cancers of the lung, colon, pancreas, prostate, and breast. Expression of Survivin also correlated with the presence of both p53 and bcl-2.

Survivin is expressed in the G2/M phase of the cell cycle. At the beginning of mitosis, Survivin associates with microtubules of mitotic spindle. Disruption of Survivin-microtubules interaction results in loss of survivin's anti-apoptotic function and increased caspse-3 activity, an important step in apoptosis. It is suggested that overexpression of Survivin in cancer may help prolong tumor cell survival by reducing apoptosis.

Interestingly, Survivin was identified by hybridization screening of human genome libraries with the cDNA of a factor Xa receptor, Effector cell Protease Receptor-1 (EPR-1). Survivin coding strand has significant sequence homology with EPR-1 suggesting a potential for functional interaction between these two proteins.

Cellular inflammatory responses and vascular injury are associated with blood coagulation and deposition of insoluble fibrin. Factor Xa is a 51 aa N-terminal peptide that is proteolytically cleaved from the inactive precursor coagulation zymogen factor X. Factor Xa plays a critical role in the coagulation process by catalyzing the activation of prothrombin to thrombin. Factor Xa acts on leukocytes, endothelium and smooth muscle cells triggering complex pathways of intracellular signaling. Factor Xa interacts with EPR-1. The full length EPR-1 predicts a protein of 337 aa (~65 kDa de-glycosylated form). EPR-1 is predicted to have 230 aa putative cysteine rich extracellular domain, 26 aa transmembrane domain, and 81 aa serine-rich cytoplasmic domain. EPR-1 is expressed in vascular endothelial cells and smooth muscle cells. Survivin and EPR-1 are encoded by structurally and topographically distinct messages from potentially originating from gene cluster at chromosome 17q25. Overexpression of EPR-1 increased apoptosis and inhibited growth of transformed cells. The molecular details and importance of the Survivin-EPR-1 interaction remains to be elucidated.

ADI has produced polyclonal antibodies to both EPR-1 and Survivin using peptides unique to each protein. The control immunogenic peptides are also available to confirm specificity of antibodies.

m=mouse; r=rat; h=human.

"Neat Antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" antibodies have been over the antigen-affinity column and recommended for immunohistochemical applications.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody competition studies.