PAXIP 1 potentiates the combination of WEE 1 inhibitor AZD 1775 and platinum agents in lung cancer Running title : PAXIP 1 potentiates WEE 1 inhibitor action

Running title: PAXIP1 potentiates WEE1 inhibitor action Ankita Jhuraney, Nicholas T. Woods, Gabriela Wright, Lily Rix, Fumi Kinose, Jodi L. Kroeger, Elizabeth Remily-Wood , W. Douglas Cress, John M. Koomen, Stephen G. Brantley, Jhanelle E. Gray, Eric B. Haura, Uwe Rix , Alvaro N. Monteiro Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA; University of South Florida Cancer Biology PhD Program, Tampa, FL, USA; Department of Drug Discovery, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA; Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA; Flow Cytometry Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA; Molecular Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA, M2Gen, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA

[1]  A. Heijink,et al.  A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity , 2015, Proceedings of the National Academy of Sciences.

[2]  P. Bunn,et al.  Recent clinical advances in lung cancer management. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Benjamin J. Raphael,et al.  Mutational landscape and significance across 12 major cancer types , 2013, Nature.

[4]  E. Iversen,et al.  Charting the Landscape of Tandem BRCT Domain–Mediated Protein Interactions , 2012, Science Signaling.

[5]  Forest M White,et al.  Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML. , 2012, Nature chemical biology.

[6]  Yunyu Shi,et al.  Structural basis of γH2AX recognition by human PTIP BRCT5‐BRCT6 domains in the DNA damage response pathway , 2011, FEBS letters.

[7]  M. Bui,et al.  MK1775, a Selective Wee1 Inhibitor, Shows Single-Agent Antitumor Activity against Sarcoma Cells , 2011, Molecular Cancer Therapeutics.

[8]  Mindy I. Davis,et al.  Comprehensive analysis of kinase inhibitor selectivity , 2011, Nature Biotechnology.

[9]  Theonie Anastassiadis,et al.  Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity , 2011, Nature biotechnology.

[10]  S. Shumway,et al.  Targeting Radiation-Induced G2 Checkpoint Activation with the Wee-1 Inhibitor MK-1775 in Glioblastoma Cell Lines , 2011, Molecular Cancer Therapeutics.

[11]  R. Medema,et al.  Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease , 2011, The Journal of cell biology.

[12]  T. Buchholz,et al.  MK-1775, a Novel Wee1 Kinase Inhibitor, Radiosensitizes p53-Defective Human Tumor Cells , 2011, Clinical Cancer Research.

[13]  P. C. de Witt Hamer,et al.  WEE1 Kinase Targeting Combined with DNA-Damaging Cancer Therapy Catalyzes Mitotic Catastrophe , 2011, Clinical Cancer Research.

[14]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[15]  Y. Hiraoka,et al.  Spatiotemporal regulations of Wee1 at the G2/M transition , 2011, Molecular biology of the cell.

[16]  H. Hirai,et al.  MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil , 2010, Cancer biology & therapy.

[17]  T. Chou.  Drug combination studies and their synergy quantification using the Chou-Talalay method. , 2010, Cancer research.

[18]  J. Bartek,et al.  The DNA-damage response in human biology and disease , 2009, Nature.

[19]  Xiaochun Yu,et al.  PTIP Regulates 53BP1 and SMC1 at the DNA Damage Sites* , 2009, The Journal of Biological Chemistry.

[20]  M. Yaffe,et al.  14-3-3 proteins, FHA domains and BRCT domains in the DNA damage response. , 2009, DNA repair.

[21]  R. Medema,et al.  The decision to enter mitosis: feedback and redundancy in the mitotic entry network , 2009, The Journal of cell biology.

[22]  John Rouse,et al.  Control of histone methylation and genome stability by PTIP , 2009, EMBO reports.

[23]  G. Superti-Furga,et al.  Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells , 2009, Leukemia.

[24]  Thomas Helleday,et al.  DNA repair pathways as targets for cancer therapy , 2008, Nature Reviews Cancer.

[25]  J. Rouse,et al.  Phospho-epitope binding by the BRCT domains of hPTIP controls multiple aspects of the cellular response to DNA damage , 2007, Nucleic acids research.

[26]  S. Kornbluth,et al.  Cdc25 and Wee1: analogous opposites? , 2007, Cell Division.

[27]  A. Doherty,et al.  Human PTIP Facilitates ATM-mediated Activation of p53 and Promotes Cellular Resistance to Ionizing Radiation* , 2004, Journal of Biological Chemistry.

[28]  Junjie Chen,et al.  Phosphopeptide Binding Specificities of BRCA1 COOH-terminal (BRCT) Domains* , 2003, Journal of Biological Chemistry.

[29]  Michael B Yaffe,et al.  BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting , 2003, Science.

[30]  Georges Mer,et al.  The BRCT Domain Is a Phospho-Protein Binding Domain , 2003, Science.

[31]  R. Kingston,et al.  Calcium Phosphate Transfection , 2003, Current protocols in cell biology.

[32]  T. Pawson,et al.  Assembly of Cell Regulatory Systems Through Protein Interaction Domains , 2003, Science.

[33]  Marc J. Prindle,et al.  BRCT Domain-Containing Protein PTIP Is Essential for Progression through Mitosis , 2003, Molecular and Cellular Biology.

[34]  Jiri Bartek,et al.  Regulation of G2/M events by Cdc25A through phosphorylation‐dependent modulation of its stability , 2002, The EMBO journal.

[35]  M. Kastan,et al.  Two Molecularly Distinct G2/M Checkpoints Are Induced by Ionizing Irradiation , 2002, Molecular and Cellular Biology.

[36]  J. Raleigh,et al.  The G(2) DNA damage checkpoint targets both Wee1 and Cdc25. , 2000, Journal of cell science.

[37]  N Watanabe,et al.  Regulation of the human WEE1Hu CDK tyrosine 15‐kinase during the cell cycle. , 1995, The EMBO journal.

[38]  P. Russell,et al.  Cell cycle regulation of human WEE1. , 1995, The EMBO journal.

[39]  Paul Nurse,et al.  Ordering S phase and M phase in the cell cycle , 1994, Cell.

[40]  T. Hunter,et al.  Cdc25M2 activation of cyclin-dependent kinases by dephosphorylation of threonine-14 and tyrosine-15. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[41]  P. Russell,et al.  Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. , 1993, The EMBO journal.

[42]  M. Igarashi,et al.  Wee1 +-like gene in human cells , 1991, Nature.

[43]  C. I. Bliss.  THE TOXICITY OF POISONS APPLIED JOINTLY1 , 1939 .