1932

Abstract

Scientific discoveries spring not only from intellect, intuition, and persistent effort but also from unforeseen circumstances, accidental observations, and chance interpersonal encounters. Unanticipated detours from intended career paths can nurture an inclination to shift one's focus and take on risk, providing the freedom to explore uncharted avenues. Here I recount some early events that transformed the directions of my own research.

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2018-03-04
2024-04-18
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Literature Cited

  1. Abbas A. 2015. A merging of minds and molecules. HHMI Bull28 http://www.hhmi.org/bulletin/spring-2015/merging-minds-and-molecules
  2. Anderson SJ, Furth ME, Wolff L, Ruscetti SK, Sherr CJ. 1982. Preparation of rat monoclonal antibodies to epitopes encoded by the viral oncogene (v-fms) of McDonough feline sarcoma virus. J. Cell Biochem. 19:275–80 [Google Scholar]
  3. Barbacid M, Lauver AV. 1981. Gene products of McDonough feline sarcoma virus have an in vitro-associated protein kinase that phosphorylates tyrosine residues: lack of detection of this enzymatic activity in vivo. J. Virol. 40:812–21 [Google Scholar]
  4. Bartek J, Bartkova J, Lukas J. 1996. The retinoblastoma protein pathway and the restriction point. Curr. Opin. Cell Biol. 8:805–14 [Google Scholar]
  5. Benveniste RE, Lieber MM, Livingston DM, Sherr CJ, Todaro GJ. et al. 1974. Infectious C-type virus isolated from a baboon placenta. Nature 248:17–20 [Google Scholar]
  6. Bowers S, Warshaw EM. 2006. Pityriasis lichenoides and its subtypes. J. Am. Acad. Dermatol. 55:557–72 [Google Scholar]
  7. Buchkovich K, Duffy LA, Harlow E. 1989. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell 58:1097–105 [Google Scholar]
  8. Chan E, Peters WP, Sweet RW, Ohno T, Kufe DW. et al. 1976. Characterisation of a virus (HL23V) isolated from cultured acute myelogenous leukaemic cells. Nature 260:266–68 [Google Scholar]
  9. Chang HW, Garon CF, Chang EH, Lowy DR, Hager GL. et al. 1980. Molecular cloning of the Harvey sarcoma virus circular DNA intermediates. II. Further structural analyses. J. Virol. 33:845–55 [Google Scholar]
  10. Chen PL, Scully P, Shew JY, Wang JYJ, Lee WH. 1989. Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell 58:1193–98 [Google Scholar]
  11. Cobrinik D, Dowdy SF, Hinds PW, Mittnacht S, Weinberg RA. 1992. The retinoblastoma protein and the regulation of cell cycling. Trends Biochem. Sci. 17:312–15 [Google Scholar]
  12. Crewdson J. 2002. Too lucky to be true. Science Fictions14–19 Boston: Little, Brown [Google Scholar]
  13. DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J. et al. 1989. The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell 58:1085–95 [Google Scholar]
  14. Donner L, Fedele LA, Garon CF, Anderson SJ, Sherr CJ. 1982. McDonough feline sarcoma virus: characterization of the molecularly cloned provirus and its feline oncogene (v-fms). J. Virol. 41:489–500 [Google Scholar]
  15. Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A. et al. 1993. Physical interaction of the retinoblastoma protein with human D cyclins. Cell 73:499–511 [Google Scholar]
  16. Downing JR, Margolis BL, Zilberstein A, Ashmun RA, Ullrich A. et al. 1989. Phospholipase C-gamma, a substrate for PDGF receptor kinase, is not phosphorylated on tyrosine during the mitogenic response to CSF-1. EMBO J 8:3345–50 [Google Scholar]
  17. Dulic V, Lees E, Reed SI. 1992. Association of human cyclin E with a periodic G1-S phase protein kinase. Science 257:1958–61 [Google Scholar]
  18. Ek B, Westermark B, Wasteson A, Heldin CH. 1982. Stimulation of tyrosine-specific phosphorylation by platelet-derived growth factor. Nature 295:419–20 [Google Scholar]
  19. Elledge SJ, Spottswood MR. 1991. A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1. EMBO J 10:2653–59 [Google Scholar]
  20. Ellis RW, Defeo D, Shih TY, Gonda MA, Young HA. et al. 1981. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature 292:506–11 [Google Scholar]
  21. Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J. et al. 1993. Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell 73:487–97 [Google Scholar]
  22. Fedele LA, Even J, Garon CF, Donner L, Sherr CJ. 1981. Recombinant bacteriophages containing the integrated transforming provirus of Gardner–Arnstein feline sarcoma virus. PNAS 78:4036–40 [Google Scholar]
  23. Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM. et al. 2015. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 16:25–35 [Google Scholar]
  24. Gallagher RE, Gallo RC. 1975. Type C RNA tumor virus isolated from cultured human acute myelogenous leukemia cells. Science 187:350–53 [Google Scholar]
  25. Hager GL, Chang EH, Chan HW, Garon CF, Israel MA. et al. 1979. Molecular cloning of the Harvey sarcoma virus closed circular DNA intermediates: initial structural and biological characterization. J. Virol. 31:795–809 [Google Scholar]
  26. Hampe A, Gobet M, Sherr CJ, Galibert F. 1984. Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. PNAS 81:85–89 [Google Scholar]
  27. Hannon GJ, Beach D. 1994. p15INK4B is a potential effector of TGF-β-induced cell cycle arrest. Nature 371:257–61 [Google Scholar]
  28. Huebner RJ, Todaro GJ. 1969. Oncogenes of RNA tumor viruses as determinants of cancer. PNAS 64:1087–94 [Google Scholar]
  29. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K. et al. 1994. A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–40 [Google Scholar]
  30. Kamijo T, Zindy F, Roussel MF, Quelle DE, Downing JR. et al. 1997. Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19 ARF. Cell 91:649–59 [Google Scholar]
  31. Kasuga M, Zick Y, Blithe DL, Crettaz M, Kahn CR. 1982. Insulin stimulates tyrosine phosphorylation of the insulin receptor in a cell-free system. Nature 298:667–69 [Google Scholar]
  32. Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. 1993. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev 7:331–42 [Google Scholar]
  33. Kim WY, Sharpless NE. 2006. The regulation of INK4/ARF in cancer and aging. Cell 127:265–75 [Google Scholar]
  34. Klein E, Klein G, Nadkarni JS, Nadkarni JJ, Wigzell H. et al. 1968. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res 28:1300–10 [Google Scholar]
  35. Koh J, Enders GH, Dynlacht BD, Harlow E. 1995. Tumour-derived p16 alleles encoding proteins defective in cell-cycle inhibition. Nature 375:506–10 [Google Scholar]
  36. Lees JA, Buchkovich KJ, Marshak DR, Anderson CW, Harlow E. 1991. The retinoblastoma protein is phosphorylated on multiple sites by human Cdc2. EMBO J 10:4279–90 [Google Scholar]
  37. Lukas J, Parry D, Aagaard L, Mann DJ, Bartkova J. et al. 1995. Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16. Nature 375:503–6 [Google Scholar]
  38. Matsushime H, Ewen ME, Strom DK, Kato JY, Hanks SK. et al. 1992. Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins. Cell 71:323–34 [Google Scholar]
  39. Matsushime H, Roussel MF, Ashmun RA, Sherr CJ. 1991. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell 65:701–13 [Google Scholar]
  40. Medema RH, Herrera RE, Lam F, Weinberg RA. 1995. Growth suppression by p16ink4 requires functional retinoblastoma protein. PNAS 92:6289–93 [Google Scholar]
  41. Meyerson M, Enders GH, Wu CL, Su LK, Gorka C. et al. 1992. A family of human cdc2-related protein kinases. EMBO J 11:2909–17 [Google Scholar]
  42. Mihara K, Cao XR, Yen A, Chandler S, Driscoll B. et al. 1989. Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product. Science 246:1300–3 [Google Scholar]
  43. Motokura T, Bloom T, Kim HG, Juppner H, Ruderman JV. et al. 1991. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature 350:512–15 [Google Scholar]
  44. Nishimura J, Huang JS, Deuel TF. 1982. Platelet-derived growth factor stimulates tyrosine-specific protein kinase activity in Swiss mouse 3T3 cell membranes. PNAS 79:4303–7 [Google Scholar]
  45. N.Y. Univ. Sch. Med. 1966. New York University School of Medicine and Post-Graduate Medical School Announcement, 1966–1967 New York: N.Y. Sch. Med. [Google Scholar]
  46. Okabe H, Gilden RV, Hatanaka M, Stephenson JR, Gallagher RE. et al. 1976. Immunological and biochemical characterisation of type C viruses isolated from cultured human AML cells. Nature 260:264–66 [Google Scholar]
  47. Oskarsson M, McClements WL, Blair DG, Maizel JV, Vande Woude GF. 1980. Properties of a normal mouse cell DNA sequence (sarc) homologous to the src sequence of Moloney sarcoma virus. Science 207:1222–24 [Google Scholar]
  48. Paul WE. 2014. Endless fascination. Annu. Rev. Immunol. 32:1–24 [Google Scholar]
  49. Phillips DR, Morrison M. 1971. Exposed protein on the intact human erythrocyte. Biochemistry 10:1766–71 [Google Scholar]
  50. Quelle DE, Zindy F, Ashmun RA, Sherr CJ. 1995. Alternative reading frames of the Ink4a tumor-suppressor gene encode two unrelated proteins capable of inducing cell-cycle arrest. Cell 83:993–1000 [Google Scholar]
  51. Racker E. 1989. A view of misconduct in science. Nature 339:91–93 [Google Scholar]
  52. Racker E, Spector M. 1981. Warburg effect revisited: merger of biochemistry and molecular biology. Science 213:303–7 [Google Scholar]
  53. Reitz MS, Miller NR, Wong-Staal F, Gallagher RE, Gallo RC. et al. 1976. Primate type-C virus nucleic acid sequences (woolly monkey and baboon types) in tissues from a patient with acute myelogenous leukemia and in viruses isolated from cultured cells of the same patient. PNAS 73:2113–17 [Google Scholar]
  54. Rettenmier CW, Chen JH, Roussel MF, Sherr CJ. 1985.a The product of the c-fms proto-oncogene: a glycoprotein with associated tyrosine kinase activity. Science 228:320–22 [Google Scholar]
  55. Rettenmier CW, Roussel MF, Quinn CO, Kitchingman GR, Look AT. et al. 1985.b Transmembrane orientation of glycoproteins encoded by the v-fms oncogene. Cell 40:971–81 [Google Scholar]
  56. Ruscetti SK, Turek LP, Sherr CJ. 1980. Three independent isolates of feline sarcoma virus code for three distinct gag-x polyproteins. J. Virol. 35:259–64 [Google Scholar]
  57. Serrano M, Hannon GJ, Beach D. 1993. A new regulatory motif in cell-cycle control causing specific-inhibition of cyclin-D/Cdk4. Nature 366:704–7 [Google Scholar]
  58. Sherr CJ. 1968. Polymorphic control of subunit synthesis for the enzyme lactate dehydrogenase in the newt, Triturus viridescens. J. Exp. Zool. 169:287–92 [Google Scholar]
  59. Sherr CJ. 1996. Cancer cell cycles. Science 274:1672–77 [Google Scholar]
  60. Sherr CJ. 2012. Ink4-Arf locus in cancer and aging. Wiley Interdiscip. Rev. Dev. Biol. 1:731–41 [Google Scholar]
  61. Sherr CJ, Baur S, Grundke I, Zeligs J, Zeligs B. et al. 1972. Cell surface immunoglobulin. 3. Isolation and characterization of immunoglobulin from nonsecretory human lymphoid cells. J. Exp. Med. 135:1392–405 [Google Scholar]
  62. Sherr CJ, Beach D, Shapiro GI. 2016. Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov 6:353–67 [Google Scholar]
  63. Sherr CJ, Fedele LA, Oskarsson M, Maizel J, Vande Woude G. 1980. Molecular cloning of Snyder-Theilen feline leukemia and sarcoma viruses: comparative studies of feline sarcoma virus with its natural helper virus and with Moloney murine sarcoma virus. J. Virol. 34:200–12 [Google Scholar]
  64. Sherr CJ, Lieber MM, Todaro GJ. 1974. Mixed splenocyte cultures and graft versus host reactions selectively induce an “S-tropic” murine type C virus. Cell 1:55–58 [Google Scholar]
  65. Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT. et al. 1985. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41:665–76 [Google Scholar]
  66. Sherr CJ, Todaro GJ. 1975. Primate type C virus p30 antigen in cells from humans with acute leukemia. Science 187:855–57 [Google Scholar]
  67. Sherr CJ, Uhr JW. 1969. Immunoglobulin synthesis and secretion. 3. Incorporation of glucosamine into immunoglobulin on polyribosomes. PNAS 64:381–87 [Google Scholar]
  68. Sherr CJ, Uhr JW. 1971. Immunoglobulin synthesis and secretion. VI. Synthesis and intracellular transport of immunoglobulin in nonsecretory lymphoma cells. J. Exp. Med. 133:901–20 [Google Scholar]
  69. Signer RA, Morrison SJ. 2013. Mechanisms that regulate stem cell aging and life span. Cell Stem. Cell 12:152–65 [Google Scholar]
  70. Spector M, Pepinsky RB, Vogt VM, Racker E. 1981. A mouse homolog to the avian sarcoma virus src protein is a member of a protein kinase cascade. Cell 25:9–21 [Google Scholar]
  71. Stehelin D, Guntaka RV, Varmus HE, Bishop JM. 1976.a Purification of DNA complementary to nucleotide sequences required for neoplastic transformation of fibroblasts by avian sarcoma viruses. J. Mol. Biol. 101:349–65 [Google Scholar]
  72. Stehelin D, Varmus HE, Bishop JM, Vogt PK. 1976.b DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170–73 [Google Scholar]
  73. Thomas L. 1956. Reversible collapse of rabbit ears after intravenous papain, and prevention of recovery by cortisone. J. Exp. Med. 104:245–52 [Google Scholar]
  74. Tsai LH, Harlow E, Meyerson M. 1991. Isolation of the human Cdk2 gene that encodes the cyclin A- and adenovirus E1a-associated p33 kinase. Nature 353:174–77 [Google Scholar]
  75. Uhr JW, Finkelstein MS. 1967. The kinetics of antibody formation. Prog. Allergy 10:37–83 [Google Scholar]
  76. Uhr JW, Pappenheimer AM Jr.. 1958. Delayed hypersensitivity. III. Specific desensitization of guinea pigs sensitized to protein antigens. J. Exp. Med. 108:891–904 [Google Scholar]
  77. Ushiro H, Cohen S. 1980. Identification of phosphotyrosine as a product of the epidermal growth factor-activated protein kinase in A-431 cell membranes. J. Biol. Chem. 255:8363–65 [Google Scholar]
  78. Vande Woude GF, Oskarsson M, Enquist LW, Nomura S, Sullivan M. et al. 1979. Cloning of integrated Moloney sarcoma proviral DNA sequences in bacteriophage λ. PNAS 76:4464–68 [Google Scholar]
  79. Varmus H. 2017. How tumor virology evolved into cancer biology and transformed oncology. Annu. Rev. Cancer 1:1–18 [Google Scholar]
  80. Vitetta ES, Baur S, Uhr JW. 1971. Cell surface immunoglobulin. II. Isolation and characterization of immunoglobulin from mouse splenic lymphocytes. J. Exp. Med. 134:242–64 [Google Scholar]
  81. Wade N. 1981. The rise and fall of a scientific superstar. N. Sci. 91:781–82 [Google Scholar]
  82. Xiong Y, Connolly T, Futcher B, Beach D. 1991. Human D-type cyclin. Cell 65:691–99 [Google Scholar]
  83. Zinkernagel RM, Doherty PC. 1979. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv. Immunol. 27:51–177 [Google Scholar]
  84. Zinkernagel RM, Doherty PC. 1997. The discovery of MHC restriction. Immunol. Today 18:14–17 [Google Scholar]
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