Anti-Securin/PTTG1 Antibody Picoband® Fluoro647 Conjugated

Securin, also known as pituitary tumor-transforming 1 or EAP1 is a protein that in humans is encoded by the PTTG1 gene. PTTG1 gene is mapped to 5q33.3. The encoded protein is a homolog of yeast securin proteins, which prevent separins from promoting sister chromatid separation. It is an anaphase-promoting complex (APC) substrate that associates with a separin until activation of the APC. The gene product has transforming activity in vitro and tumorigenic activity in vivo, and the gene is highly expressed in various tumors. The gene product contains 2 PXXP motifs, which are required for its transforming and tumorigenic activities, as well as for its stimulation of basic fibroblast growth factor expression. It also contains a destruction box (D box) that is required for its degradation by the APC. The acidic C-terminal region of the encoded protein can act as a transactivation domain. The gene product is mainly a cytosolic protein, although it partially localizes in the nucleus.

A synthetic peptide corresponding to a sequence at the C-terminus of human Securin, different from the related rat sequence by four amino acids, and from the related mouse sequence by five amino acids.

Expressed at low level in most tissues, except in adult testis, where it is highly expressed. Overexpressed in many patients suffering from pituitary adenomas, primary epithelial neoplasias, and esophageal cancer. .

Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation. .

1. Holt, L. J., Krutchinsky, A. N., Morgan, D. O. Positive feedback sharpens the anaphase switch. Nature 454: 353-357, 2008. 2. Ying, H., Furuya, F., Zhao, L., Araki, O., West, B. L., Hanover, J. A., Willingham, M. C., Cheng, S. Aberrant accumulation of PTTG1 induced by a mutated thyroid hormone beta-receptor inhibits mitotic progression. J. Clin. Invest. 116: 2972-2984, 2006.