PIN1


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PIN1

A gene on chromosome 19p13 that encodes an essential peptidylprolyl isomerase, which regulates mitosis by interacting with NIMA and downregulating its mitosis-promoting activity. PIN1 downregulates BTK’s kinase activity, transactivates multiple oncogenes and induces centrosome amplification, chromosome instability and cell transformation. PIN1 is required for efficient dephosphorylation and recycling of RAF1 after mitogen activation.
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Recent studies have shown that treatment of cells with pin1 inhibitor juglone delays the growth of various tumour cell lines (187), suggesting that inhibition of pin1 can be used as an approach for inhibiting tumour growth.
Targeting carcinogenesis: a role for the prolyl isomerase Pin1? Mol Carcinog 2006; 45: 397-402.
Mutations in proline 82 of p53 impair its activation by PIN1 and ChK2 in response to DNA damage.
Normally, tau's protector, Pin1, keeps it from falling in with hardened tangles.
Lu and his colleagues have found a variation in the Pin1 promoter, a stretch of DNA that controls activity of the gene, associated with a five-year later onset of Alzheimer's disease.
In 1995, Kun Ping Lu of Beth Israel Deaconess Medical Center in Boston and Tony Hunter of the Salk Institute for Biological Studies in La Jolla, Calif., discovered Pin1. They subsequently showed that it interacts with a protein called tau, an important component of one of the two brain lesions seen in Alzheimer's disease.
Lu, Hunter, and their colleagues had shown that Pin1 binds to tau overloaded with phosphates.
We localized Pin1 to dendritic rafts and to the PSD and found a pathological loss of Pin1 within the synapses of AD patient brains.
Pin1, Phosphorylated Tau, Oligomers of A[beta], and Glutamate Receptor Coincidently Exist in Detergent-Resistant Dendritic Rafts and PSD Fractions.
Cho, "The role of PIN1 on odontogenic and adipogenic differentiation in human dental pulp stem cells," Stem Cells and Development, vol.
Gutkind, "Regulation of the transcriptional activity of c-Fos by ERK: a novel role for the prolyl isomerase Pin1," The Journal of Biological Chemistry, vol.
Using a proteomic approach, the prolyl isomerase PIN1 was found to be particularly sensitive to oxidative damage, being highly downregulated and oxidized in hippocampus of AD patients [44].