TABLE 1.
List of Pin1 substrates in transcription regulation.
| Substrates | Motif | Regulation by Pin1 | Cellular consequence of Pin1 interaction | Evidence of isomerization | References |
| Transcription factors | |||||
| (1) Nucleocytoplasmic shuttling | |||||
| RelA | T254 | Increased nuclear accumulation and stability | Cell survival, proliferation and inflammation | Yes | Ryo et al., 2003; Atkinson et al., 2009; Fan et al., 2009; Shinoda et al., 2015 |
| β-catenin | S246 | Increased nuclear accumulation and stability | Cancer cell proliferation, osteogenesis | Yes | Ryo et al., 2001; Nakamura et al., 2012 |
| Fox04 | N/A | Deubiquitylation and decreased nuclear accumulation | Cell cycle and cancer cell proliferation | Yes | Brenkman et al., 2008 |
| NFAT | N/A | Decreased nuclear accumulation | T cell activation | N/A | Liu et al., 2001 |
| (2) Protein stability | |||||
| p53 | S33, S46, T81, S315 | Increased stability and transactivation | DNA damage response, cancer cell cycle arrest and apoptosis | Yes | Wulf et al., 2002; Zacchi et al., 2002; Zheng et al., 2002 |
| p63 | T538 | Increased or decreased stability | Cancer and limb development | N/A | Li et al., 2013; Restelli et al., 2014 |
| p73 | S412, T442, T482 | Increased stability and transactivation | Apoptosis | Yes | Mantovani et al., 2004 |
| c-Jun | S63, S73 | Increased stability | Ras and JNK signaling | Yes | Wulf et al., 2001; Pulikkan et al., 2010 |
| Naong | S52, S65, S71, T287 | Increased stability | Stem cell pluripotency | Yes | Moretto-Zita et al., 2010 |
| Oct4 | S12 | Increased stability | Stem cell pluripotency | Yes | Nishi et al., 2011 |
| FoxMl | S331, S704 | Increase stability | Drug resistance | N/A | Kruiswijk et al., 2016; Wang et al., 2016 |
| Osterix | S76, S80 | Increase stability and transactivation | Osteogenic differentiation | Yes | Jang et al., 2005 |
| ATF1 | T184 | Increase stability and transactivation | NPC tumorigenesis | N/A | Huang et al., 2016 |
| TR3 | S95, S140, S431 | Increase stability and transactivation | Mitogenesis | Yes | Chen et al., 2012 |
| Runx2 | T408, T449, S472, S510 | Increase sub-nuclear area accumulation and stability | Skeletal development, Osteoblast differentiation. | Yes | Lee et al., 2013; Yoon et al., 2013 |
| Runx3 | T209, T212, T231, S214 | Degradation, suppresses transactivation | Breast cancer cell proliferation | Yes | Nicole Tsang et al., 2013 |
| Smad3 | T179, S204, S208, S213 | Decreased stability | Cell migration and invasion | Yes | Nakano et al., 2009 |
| IRF3 | S339 | Decreased stability | Antiviral responses | Yes | Saitoh et al., 2006 |
| RAR | S77 | Decreased stability | Cancer cell proliferation | Yes | Gianni et al., 2009 |
| MEF2C | S98, S110 | Decreased stability | Muscle terminal differentiation | Yes | Magli et al., 2010 |
| Fox03 | N/A | Decreased stability | Drug resistance | No | Shimizu et al., 2016 |
| (3) DNA binding activity and transcriptional activity | |||||
| c-Myc | T58, S62 | Decreased stability, increased DNA binding | Cancer cell proliferation | Yes | Yeh et al., 2004; Farrell et al., 2013 |
| ERα | S118, S294 | Increased dimerization, stability and transactivation activity | Cancer cell proliferation | Yes | Rajbhandari et al., 2014 |
| HIFIα | S641, S643 | Increase stability and transactivation | Angiogenesis | Yes | Jalouli et al., 2014; Han H. J. et al., 2016 |
| SP1 | T739 | Increased stability, decreased DNA binding | Cell cycle progression | Yes | Yang et al., 2014 |
| c-Fos | T232, T325, T331 | Increased interaction with other transcription factors | Mitogen response | Yes | Monje et al., 2005 |
| GR | S203, S211 | Increased transactivation | Inflammatory response | Yes | Poolman et al., 2013 |
| PPARγ | S273 | Increased stability and transactivation | Adipogenesis | N/A | Fujimoto et al., 2010; Han Y. et al., 2016 |
| Nur77 | S152 | Increased DNA binding and transactivation | Vascular disease and metabolism | No | van Tiel et al., 2012 |
| Stat3 | S272 | Increased DNA binding and transactivation | EMT and type 2 diabetes | No | Lufei et al., 2007; Lv et al., 2013; Nakada et al., 2019 |
| Transcription cofactors | |||||
| SRC-3 | multiple sites | Increased interaction with p300 and degradation | Brease cancer cell proliferation | Yes | Yi et al., 2005 |
| Notch1 | S2122, T2133, S2137 | Enhanced Notch1 cleavage and transcriptional activity | Notch signaling | Yes | Rustighi et al., 2009 |
| SMRT | S1241, S1445, S1469 | Decreased stability | Cancer cell proliferation and response to tamoxifen | Yes | Stanya et al., 2008 |
| CRTC2 | S136 | Decreased nuclear accumulation | Glucose metabolism | N/A | Nakatsu et al., 2010 |
| PRDM16 | N/A | Decreased stability | Thermogenesis | N/A | Chi and Cohen, 2016 |
| RNA polymerase | |||||
| Rpbl | S2, S5 of CTD | Altered phosphorylation of CTD | Transcription | Yes | Xu et al., 2003; Zhang et al., 2012 |
| Histone | |||||
| Histone HI | multiple sites | Increased dephosphorylation and binding to chromatin | Transcription | Yes | Raghuram et al., 2013 |
| Transcription elongation regulators | |||||
| Spt5 | multiple sites | Increased binding to transcription regulators | Transcription | N/A | Lavoie et al., 2001 |
| Brd4 | T204 | Increased stability and transcriptional activity | Transcription and cancer | Yes | Hu et al., 2017 |
| mRNA decay factors | |||||
| SLBP | T171 | Increased dephosphorylation | Cell cycle | Yes | Krishnan et al., 2012 |
| AUF1 | S83 | Decreased AUF1-mRNA interactions | Eosinophil survival, T cell activation, allergic inflammation | Yes | Shen et al., 2005; Esnault et al., 2006 |
| KSRP | S181 | Increased dephosphorylation and mRNA interaction | Hyperparathyroidism | N/A | Nechama et al., 2009 |
| HuR | N/A | mRNA binding affinity | Transcription | N/A | Krishnan et al., 2014 |