peptidyl-prolyl cis-trans isomerase NIMA-interacting 1; peptidyl-prolyl cis-trans isomerase Pin1; PPIase Pin1; Rotamase Pin1 (PIN1)
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Function
- Pin-1 regulates conformation & function of some phosphorylated proteins including microtubule associated protein tau, & is involved in regulation of mitosis
- phosphorylation inactivates pin1
- Pin1 catalyzes prolyl isomerization of specific phospho-Ser/Thr-Pro motifs in[2][4]:
- Cdc25C
- microtubule associated protein tau - interaction site on tau is phospho-Thr231-Pro232[7]
- NIMA
- wee1
- plk1
- myt1
- cdc27
- CENP-F
- Incenp
- rab4
- bcl-2
- NHERF-1
- KRMP1
- RNA polymerase II
- sin3-rpd3
- c-jun
- beta-catenin - inhibits interaction with APC
- cyclin D1 - both transcriptional & post-translational levels, increases stability & c-jun targeted transcriptional activity of cyclin D1
- DNA damage enhances the interaction of Pin-1 & p53; this is dependent on the WW domain in pin-1 & Ser33/46 in p53
- Pin-1 regulates stability of p53 & its p21 transcriptional activity
- loss of pin-1 in vitro results in loss of p53 & p21 responses to DNA damage
Expression
- expressed at low levels in most normal tissues
- expression is increased with cell proliferation
Pathology
- Pin1 expression inversely correlates with neuronal vulnerability & neurofibrillary degeneration in Alzheimer's disease.
- Pin1 knockout mice show progressive age dependent neuropathy with motor & behavioral defects, tau hyperphosphorylation, tau filament formation & neurodegeneration[3]
- Pin1 is overexpressed in some cancers
More general terms
- peptidyl-prolyl cis/trans isomerase, NIMA-interacting (Pin)
- peptidyl-prolyl cis/trans isomerase (PPIase) or rotamase
- phosphoprotein
Additional terms
References
- ↑ Wulf GM et al, Role of Pin1 in the regulation of p53 stability and p21 transactivation, and cell cycle checkpoints in response to DNA damage. J Biol Chem 277:47976-9, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11090625 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12388558
- ↑ 2.0 2.1 Zhou XZ, Kops O, Werner A, Lu PJ, Shen M, Stoller G, Kullertz G, Stark M, Fischer G, Lu KP. Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. Mol Cell. 2000 Oct;6(4):873-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11090625
- ↑ 3.0 3.1 Liou YC et al, Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424:556-60, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12891359
- ↑ 4.0 4.1 Lu KP, Liou YC, Zhou XZ. Pinning down proline-directed phosphorylation signaling. Trends Cell Biol. 2002 Apr;12(4):164-72. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11978535
- ↑ Lu KP Prolyl isomerase Pin1 as a molecular target for cancer diagnostics and therapeutics. Cancer Cell. 2003 Sep;4(3):175-80. Review. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/14522251
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5300
- ↑ 7.0 7.1 Smet C, Sambo AV, Wieruszeski JM, Leroy A, Landrieu I, Buee L, Lippens G. The peptidyl prolyl cis/trans-isomerase Pin1 recognizes the phospho-Thr212-Pro213 site on Tau Biochemistry 43(7):2032-40, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14967043
- ↑ Bao L, Kimzey A, Sauter G, Sowadski JM, Lu KP, Wang DG. Prevalent overexpression of prolyl isomerase Pin1 in human cancers Am J Pathology 164(5):1727-37, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15111319