PTTG1
Description
The PTTG1 (PTTG1 regulator of sister chromatid separation, securin) is a protein-coding gene located on chromosome 5.
Securin, encoded by the PTTG1 gene in humans, is a protein homologous to yeast securin proteins that prevent separins from promoting sister chromatid separation. It acts as an anaphase-promoting complex (APC) substrate, associating with a separin until APC activation. PTTG1 possesses transforming activity in vitro and tumorigenic activity in vivo, with high expression in various tumors. It contains two PXXP motifs essential for its transforming and tumorigenic activities, as well as for stimulating basic fibroblast growth factor expression. PTTG1 also features a destruction box (D box) required for its degradation by the APC. The encoded protein's acidic C-terminal region can act as a transactivation domain. PTTG1 mainly resides in the cytosol but partially localizes in the nucleus. PTTG1 interacts with DNAJA1, Ku70, P53, PTTG1IP, and RPS10. During mitosis, CDK1 phosphorylates PTTG1 at Ser-165. PTTG1 expression is downregulated in melanoma cells in response to the cyclin-dependent kinase inhibitor PHA-848125.
PTTG1, also known as Securin, plays a critical role in maintaining chromosome stability, regulating the p53/TP53 pathway, and participating in DNA repair. It acts by inhibiting the activity of key proteins, including Separase/ESPL1. During mitosis, PTTG1 blocks Separase function, preventing the breakdown of the cohesin complex and subsequent chromosome segregation. At the onset of anaphase, PTTG1 undergoes ubiquitination, leading to its degradation and the release of ESPL1. While PTTG1 acts as an inhibitor, it is also essential for activating ESPL1. PTTG1 negatively regulates the transcriptional activity and apoptosis-inducing function of TP53. This negative regulation of TP53 might contribute to the protein's potent transforming capabilities when overexpressed. PTTG1 may also participate in DNA repair through its interaction with Ku, potentially linking DNA damage response pathways to sister chromatid separation.
PTTG1 is also known as EAP1, ECRAR, HPTTG, PTTG, TUTR1.
