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| Untersuchte Arbeit: Seite: 31, Zeilen: 1 ff. (entire page) |
Quelle: Rizzolio 2010 Seite(n): 29, 30, 31, Zeilen: 29: 7 f.f - 30:1-2.5 ff. - 31:1-3 |
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| PIN1 is a member of the evolutionarily conserved peptidylprolyl isomerase (PPIase) family of proteins. PIN1 has a two-domain structure that consists of an N-terminal WW domain (amino acids 1–39) and the Cterminal PPIase domain (amino acids 45–163). The WW domain binds only to specific pSer/Thr-Pro-motifs and the PPIase isomerase domain catalyzes the conformational switch from cis to trans of target proteins. This fact is especially important because Pro-directed kinases and phosphatases are conformation-specific and act only on the trans isoform (55,56). For this reason, PIN1 is important for many physiological activities of the cell (Fig. 4).
In cell cycle control, PIN1 was originally identified and defined as a protein important in mitosis (57). Depletion of PIN1 in yeast and human cells induces mitotic arrest and its over-expression blocks the cells in the G2 phase of the cell cycle (51). Since the discovery of PIN1, a plethora of protein targets have been discovered, many of which are involved in the G0 and G1/S control (58). PIN1 controls Cyclin D1 mRNA levels and it is involved in regulation of CyclinD1, c-MYC and Cyclin E protein stability. PIN1 -/- MEF showed proliferative defects in cell cycle entry after serum deprivation. In addition, PIN1 is a target of E2F transcription factors and its mRNA and protein levels fluctuate during cell cycle [(59).] 51)Lu, K. P., Hanes, S. D., and Hunter, T. A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature (Lond.), 380: 544–547, 1996. 55) Lu, K.P., et al., Prolyl cistrans isomerization as a molecular timer. Nat Chem Biol, 2007. 3(10): p. 619‐29. 56) Lu, K.P. and X.Z. Zhou, The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease. Nat Rev Mol Cell Biol, 2007. 8(11): p. 904‐16. 57) Shen, M., et al., The essential mitotic peptidylprolyl isomerase Pin1 binds and regulates mitosisspecific phosphoproteins. Genes Dev, 1998. 12(5): p. 706‐20. 58) Yeh, E.S. and A.R. Means, PIN1, the cell cycle and cancer. Nat Rev Cancer, 2007. 7(5): p. 381‐8. 59) Ryo, A., et al., PIN1 is an E2F target gene essential for Neu/Rasinduced [sic] transformation of mammary epithelial cells. Mol Cell Biol, 2002. 22(15): p. 5281‐95. |
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PIN1 is a member of the evolutionarily conserved peptidylprolyl isomerase (PPIase) family of proteins. PIN1 has a two-domain structure that consists of an N-terminal WW domain (amino acids 1–39) and the Cterminal PPIase domain (amino acids 45–163). The WW domain binds only to specific pSer/Thr-Pro-motifs and the PPIase isomerase domain catalyzes the conformational switch from cis to trans of target proteins. This fact is especially important because Pro-directed kinases and phosphatases are conformation-specific and act only on the trans isoform [3, 4]. For this reason, PIN1 is important for many physiological activities of the cell (Fig. 1). [Page 30] In cell cycle control, PIN1 was originally identified and defined as a protein important in mitosis. Many of PIN1’s substrates contain a single phosphorylation target in the form of CDC25, WEE1 and RPB1[15]. Others, like CK2 and Sil, have multi-phosphorylation sites, suggesting a different mechanism in PIN1 function [16, 17]. Depletion of PIN1 in yeast and human cells induces mitotic arrest and its over-expression blocks the cells in the G2 phase of the cell cycle [14]. Since the discovery of PIN1, a plethora of protein targets have been discovered, many of which are involved in the G0 and G1/S control [11]. Evidence emerged from in vitro and in vivo animal models. PIN1 controls Cyclin D1 mRNA levels and it is involved in regulation of CyclinD1, c-MYC and Cyclin E protein stability [5, 11]. PIN1 -/- MEF showed [Page 31] proliferative defects in cell cycle entry after serum deprivation. In addition, PIN1 is a target of E2F transcription factors and its mRNA and protein levels fluctuate during cell cycle [18]. 3. Lu, K.P., et al., Prolyl cistrans isomerization as a molecular timer. Nat Chem Biol, 2007. 3(10): p. 619‐29. 4. Lu, K.P. and X.Z. Zhou, The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease. Nat Rev Mol Cell Biol, 2007. 8(11): p. 904‐16. 11. Yeh, E.S. and A.R. Means, PIN1, the cell cycle and cancer. Nat Rev Cancer, 2007. 7(5): p. 381‐8. 14. Lu, K.P., S.D. Hanes, and T. Hunter, A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature, 1996. 380(6574): p. 544‐7. 15. Shen, M., et al., The essential mitotic peptidylprolyl isomerase Pin1 binds and regulates mitosisspecific phosphoproteins. Genes Dev, 1998. 12(5): p. 706‐20. 16. Messenger, M.M., et al., Interactions between protein kinase CK2 and Pin1. Evidence for phosphorylation-dependent interactions. J Biol Chem, 2002. 277(25): p. 23054‐64. 17. Campaner, S., et al., Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint. Mol Cell Biol, 2005. 25(15): p. 6660‐72. 18. Ryo, A., et al., PIN1 is an E2F target gene essential for Neu/Ras-induced transformation of mammary epithelial cells. Mol Cell Biol, 2002. 22(15): p. 5281‐95. |
Although identical, nothing has been marked as a citation. Starting with reference 55), again the formatting of references changes in Rlm so that it becomes exactly like that of the unnamed source. "Neu/Rasinduced" (missing hyphen) is a copy-and-paste-mistake. |
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