23. Chen J, Marechal V, Levine AJ (1993) Mapping of the p53 and mdm-2 interaction domains. Mol Cell Biol 13: 4107–4114. 24. Suetsugu S, Murayama K, Sakamoto A, Hanawa-Suetsugu K, Seto A, Oikawa T, et al. (2006) The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent membrane deformation. J Biol Chem 281: 35347–35358. 25. Levine AJ, Oren M (2009) The first 30 years of p53: growing ever more complex. Nat Rev Cancer 9: 749–758. 26. Laine A, Ronai Z (2007) Regulation of p53 localization and transcription by the HECT domain E3 ligase WWP1. Oncogene 26: 1477–1483. 27. Laine A, Topisirovic I, Zhai D, Reed JC, Borden KL, Ronai Z (2006) Regulation of p53 localization and activity by Ubc13. Mol Cell Biol 26: 8901–8913. 28. Andrews P, He YJ, Xiong Y (2006) Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53 and promotes cell growth by antagonizing p53 function. Oncogene 25: 4534–4548. 29. Yuan J, Luo K, Zhang L, Cheville JC, Lou Z (2010) USP10 regulates p53 localization and stability by deubiquitinating p53. Cell 140: 384–396. 30. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, et al. (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274: 948–953. 31. Sakaguchi K, Saito S, Higashimoto Y, Roy S, Anderson CW, et al. (2000) Damage-mediated phosphorylation of human p53 threonine 18 through a cascade mediated by a casein 1-like kinase. Effect on Mdm2 binding. J Biol Chem 275: 9278–9283. 32. Ma J, Martin JD, Zhang H, Auger KR, Ho TF, et al. (2006) A second p53 binding site in the central domain of Mdm2 is essential for p53 ubiquitination. Biochemistry 45: 9238–9245. 33. Yu GW, Rudiger S, Veprintsev D, Freund S, Fernandez-Fernandez MR, et al. (2006) The central region of HDM2 provides a second binding site for p53. Proc Natl Acad Sci U S A 103: 1227–1232. 34. Wallace M, Worrall E, Pettersson S, Hupp TR, Ball KL (2006) Dual-site regulation of MDM2 E3-ubiquitin ligase activity. Mol Cell 23: 251–263. 35. Argentini M, Barboule N, Wasylyk B (2001) The contribution of the acidic domain of MDM2 to p53 and MDM2 stability. Oncogene 20: 1267–1275. IRTKS Regulates MDM2-Mediated p53 Ubiquitination 36. Shimizu H, Burch LR, Smith AJ, Dornan D, Wallace M, et al. (2002) The conformationally flexible S9–S10 linker region in the core domain of p53 contains a novel MDM2 binding site whose mutation increases ubiquitination of p53 in vivo. J Biol Chem 277: 28446–28458. 37. Bothner B, Lewis WS, DiGiammarino EL, Weber JD, Bothner SJ, et al. (2001) Defining the molecular basis of Arf and Hdm2 interactions. J Mol Biol 314: 263–277. 38. Lohrum MA, Ashcroft M, Kubbutat MH, Vousden KH (2000) Contribution of two independent MDM2-binding domains in p14(ARF) to p53 stabilization. Curr Biol 10: 539–542. 39. Dai MS, Zeng SX, Jin Y, Sun XX, David L, et al. (2004) Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition. Mol Cell Biol 24: 7654–7668. 40. Jin A, Itahana K, O’Keefe K, Zhang Y (2004) Inhibition of HDM2 and activation of p53 by ribosomal protein L23. Mol Cell Biol 24: 7669–7680. 41. Zhang Y, Wolf GW, Bhat K, Jin A, Allio T, et al. (2003) Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway. Mol Cell Biol 23: 8902–8912. 42. Takagi M, Absalon MJ, McLure KG, Kastan MB (2005) Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin. Cell 123: 49–63. 43. Zhu Y, Poyurovsky MV, Li Y, Biderman L, Stahl J, et al. (2009) Ribosomal protein S7 is both a regulator and a substrate of MDM2. Mol Cell 35: 316–326. 44. Roger L, Gadea G, Roux P (2006) Control of cell migration: a tumour suppressor function for p53? Biol Cell 98: 141–152. 45. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, et al. (2003) Cell migration: integrating signals from front to back. Science 302: 1704–1709. 46. Zuchero JB, Coutts AS, Quinlan ME, Thangue NB, Mullins RD (2009) p53- cofactor JMY is a multifunctional actin nucleation factor. Nat Cell Biol 11: 451–459. 47. Coutts AS, Weston L, La Thangue NB (2009) A transcription co-factor integrates cell adhesion and motility with the p53 response. Proc Natl Acad Sci U S A 106: 19872–19877. PLoS ONE | www.plosone.org 12 August 2011 | Volume 6 | Issue 8 | e23571