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Maturation-promoting factor in the early days
A common refrain these days at scien- (dating back to Boveri tific meetings and seminars on cellcycle control is ‘Boy,the cell cycle sure is complicated!’Indeed, the complexity of celkycle control in terms of com- attention on events of ponents, checkpoints and positive and vation, the basic mes ck loops has become a entry into the field by new graduate students and postdoctoral r~e~chers, who often think all the available avenues of work are fully saturated and ruthlessly competitive. was not always so. The study of mat , whose ration-promoting factor characterization ju rent frenzied activi
i
cipally interested in de the control of cell fate by
tic cell could induce
on’s observatfon in owever, it was essen velop conditions for in
which assembledthe historical evidence oocytes after progesterone
I believed the answer to MPF action 0 1995,ElsevierScience Ltd 0968~0004/95/$09.50
autoa~pli~catio~
of
it is possible that initial activation of the der the control of the
for entertaining such a hypothesis was the example of rabbit muscle phosAt that time, no one in Krebs’*iab phorylase kinase, t e first protein worked on cells; the focus was on kinase studied, whit could undergo purification and biochemical charac- autoactivation by autophosphorylat~o~ terization of enzymes from rabbit skel- in a reaction highly dependent on efore several laetal muscle. These were available in whether f%-glycerophosphate (f3GP)was quantities suita for microinjection present in the reactionrG. could cause GVBDif oocytes were pre, work. However, ebs himself bad a ge of physiology and was larger questions than ication and cbaracterizto talk at length about ’ but never lost sight of experimental inter- ments were carried out to inject protein kinase cou the study of glyco- phosphorylase kinase (Phb gen metabolism and CAMPaction was a oocytes with measurement of total phoshot area at that time, no one worried phorylation. There was no immediate
Initiator
d in the induction of 1975 scheme of cytoplasmic mechanisms inv (WBD) in Xenopkls oocytes. (1) Progesterone acts on the receptor local oocyte; (2) the synthesis of the ‘initiator’ is induced: (3) t promoting Gxtor (MPF) to transform it into the active for Drecursor molecules: (5) active MPF near the nuclear m breakdown. Reproduced with
thqe was an increasi of its generalimportance.Synchroniz tissue culturecells were foundto exh s most easily seen In highly
and Markert, C. L. (1.973) 1. 177,x29-145 2 Johnson, R. T. and Rao, P. M. (1970) Nafore orphol. 20,401-414 4 5 6 Brury, K. C. and Schorderet-Slatkine, Q/I 4,266-274 7 fvlorrill, G. A. and Murphy, J. 6. (1972) Nature 236282-284 . and Gerhart, J. C. (1977)
proportional to the final concentration PF in the system, bypassing an ficable and cumbersome volume dependence of activity in the microinjection assay*O,and the all-or-none character of GVBD.Thus, a unit of could be defined. Despite the exci ng the cell-freesyste to use it to learn somemitosis. We were not to initiate efforts to !F using the cell-free system because of the long history of failure by others. This history also made it imprudent to propose purification in
Ilier, G. and Picard, A. (1983)
possess histone Wl kinase activity,
both assay systems without any appar-
as Cdc2 and cyclin B (Refs 39,40). The fractions that had appeared active
10 Heidemann, S. R. and Kirschner, IV. W. (1975) 1. Cell Mol. 67, 105-117 11 Gautier, J. and Maller, J. L. (1991) EM50 J. 10, 177-182 12 Izumi, T., Walker, D. H. and Mailer, J. L. (1992) Mol. Biol. Cell. 3,927-939 13 Hoffman, I. et al. (1993) EMBO J. 12, 53-64 14 Krebs, E. G. and Fischer, E. H. (1956) Biochim. Biophys. Acta 20,150-156 15 Walsh, Q. A., Perkins, J. P. and Krebs, (1968) J. Biol. Chem. 243,3763-3765 16 Wang, J. H., Stull, J. T., Huang, T. S. and Krebs, E. 6. (1976) J. Biol. Chem. 251, 4521-4527 27 Wassermann, W. J. and Smith, L. Q. (1981) J. Cell Dial. 89,389-395
38 19
asui, Y. (1976) 191,
1266-1266 10 Wu, M. and Gerhart, J. C. (1980) Dev. BioL 79, 465-477 21 M&r, J. L. and Krebs, E. G. (1977) R Biok Chem. 252,1712-1718 and Butcher, F. R. (1977) Alature 22 her, F. R. and Krebs, E. G. (1979) J. &I/, &em. 254,579-562 24 Sadler, S. E. and Mater, J. L. (1985) AC&.Cyclicivuo/. Prw. was. Res. 19.179-194 2!j AnidorNepicard, J., Schorderet-Slatkine, S., Hanoune, J. and Baulieu, E. E. (1981) Nature 292,255-257 Jordana, X,, Allende, C. C. and Allende, J. E. (1981) Biochem. /nN3,527-532 23
;ZP Wassermann, W. J . and asui, Y. (1975) Ew. Cell Ms. 91,3&I.-368 2968) Nature 335,519-625 . L. and Vande Woude, G. F. 30 Sunkara, P. S., Wright, D. A. and Rao, P. N. (1979) Proc. Nat/ Acad. Sci. US4 76.
33 Bradbury, E. FBI.,Inglis, R. J. and Matthews, H. R. (1974) Nature 247,257-261 34 Chambers, T. C. and Langan, T. A. (1990) J. Biol. em. 265,16940-16947 35 Lohka, . and Masui, Y. (1983) Science 220, 719-7 36 Lohka, M. J. and Mailer, J. L. (1985) J. Ceil 101,51S-523
suppressor genes in a
Reading a textbook from cover to cover is
are activated or in human tumours
aiity and excessive
e evolution of the ideas as
new chapterdevoted to tumour
material, the more recent topics covere in the second edition are less personalized, presumably because it is too early to judge which are the most
symposia?) organiz Society, a society founded several years ago to provide a forum for the born-again
i
cipally interested in de the control of cell fate by
tic cell could induce
on’s observatfon in owever, it was essen velop conditions for in
which assembledthe historical evidence oocytes after progesterone
I believed the answer to MPF action 0 1995,ElsevierScience Ltd 0968~0004/95/$09.50
autoa~pli~catio~
of
it is possible that initial activation of the der the control of the
for entertaining such a hypothesis was the example of rabbit muscle phosAt that time, no one in Krebs’*iab phorylase kinase, t e first protein worked on cells; the focus was on kinase studied, whit could undergo purification and biochemical charac- autoactivation by autophosphorylat~o~ terization of enzymes from rabbit skel- in a reaction highly dependent on efore several laetal muscle. These were available in whether f%-glycerophosphate (f3GP)was quantities suita for microinjection present in the reactionrG. could cause GVBDif oocytes were pre, work. However, ebs himself bad a ge of physiology and was larger questions than ication and cbaracterizto talk at length about ’ but never lost sight of experimental inter- ments were carried out to inject protein kinase cou the study of glyco- phosphorylase kinase (Phb gen metabolism and CAMPaction was a oocytes with measurement of total phoshot area at that time, no one worried phorylation. There was no immediate
Initiator
d in the induction of 1975 scheme of cytoplasmic mechanisms inv (WBD) in Xenopkls oocytes. (1) Progesterone acts on the receptor local oocyte; (2) the synthesis of the ‘initiator’ is induced: (3) t promoting Gxtor (MPF) to transform it into the active for Drecursor molecules: (5) active MPF near the nuclear m breakdown. Reproduced with
thqe was an increasi of its generalimportance.Synchroniz tissue culturecells were foundto exh s most easily seen In highly
and Markert, C. L. (1.973) 1. 177,x29-145 2 Johnson, R. T. and Rao, P. M. (1970) Nafore orphol. 20,401-414 4 5 6 Brury, K. C. and Schorderet-Slatkine, Q/I 4,266-274 7 fvlorrill, G. A. and Murphy, J. 6. (1972) Nature 236282-284 . and Gerhart, J. C. (1977)
proportional to the final concentration PF in the system, bypassing an ficable and cumbersome volume dependence of activity in the microinjection assay*O,and the all-or-none character of GVBD.Thus, a unit of could be defined. Despite the exci ng the cell-freesyste to use it to learn somemitosis. We were not to initiate efforts to !F using the cell-free system because of the long history of failure by others. This history also made it imprudent to propose purification in
Ilier, G. and Picard, A. (1983)
possess histone Wl kinase activity,
both assay systems without any appar-
as Cdc2 and cyclin B (Refs 39,40). The fractions that had appeared active
10 Heidemann, S. R. and Kirschner, IV. W. (1975) 1. Cell Mol. 67, 105-117 11 Gautier, J. and Maller, J. L. (1991) EM50 J. 10, 177-182 12 Izumi, T., Walker, D. H. and Mailer, J. L. (1992) Mol. Biol. Cell. 3,927-939 13 Hoffman, I. et al. (1993) EMBO J. 12, 53-64 14 Krebs, E. G. and Fischer, E. H. (1956) Biochim. Biophys. Acta 20,150-156 15 Walsh, Q. A., Perkins, J. P. and Krebs, (1968) J. Biol. Chem. 243,3763-3765 16 Wang, J. H., Stull, J. T., Huang, T. S. and Krebs, E. 6. (1976) J. Biol. Chem. 251, 4521-4527 27 Wassermann, W. J. and Smith, L. Q. (1981) J. Cell Dial. 89,389-395
38 19
asui, Y. (1976) 191,
1266-1266 10 Wu, M. and Gerhart, J. C. (1980) Dev. BioL 79, 465-477 21 M&r, J. L. and Krebs, E. G. (1977) R Biok Chem. 252,1712-1718 and Butcher, F. R. (1977) Alature 22 her, F. R. and Krebs, E. G. (1979) J. &I/, &em. 254,579-562 24 Sadler, S. E. and Mater, J. L. (1985) AC&.Cyclicivuo/. Prw. was. Res. 19.179-194 2!j AnidorNepicard, J., Schorderet-Slatkine, S., Hanoune, J. and Baulieu, E. E. (1981) Nature 292,255-257 Jordana, X,, Allende, C. C. and Allende, J. E. (1981) Biochem. /nN3,527-532 23
;ZP Wassermann, W. J . and asui, Y. (1975) Ew. Cell Ms. 91,3&I.-368 2968) Nature 335,519-625 . L. and Vande Woude, G. F. 30 Sunkara, P. S., Wright, D. A. and Rao, P. N. (1979) Proc. Nat/ Acad. Sci. US4 76.
33 Bradbury, E. FBI.,Inglis, R. J. and Matthews, H. R. (1974) Nature 247,257-261 34 Chambers, T. C. and Langan, T. A. (1990) J. Biol. em. 265,16940-16947 35 Lohka, . and Masui, Y. (1983) Science 220, 719-7 36 Lohka, M. J. and Mailer, J. L. (1985) J. Ceil 101,51S-523
suppressor genes in a
Reading a textbook from cover to cover is
are activated or in human tumours
aiity and excessive
e evolution of the ideas as
new chapterdevoted to tumour
material, the more recent topics covere in the second edition are less personalized, presumably because it is too early to judge which are the most
symposia?) organiz Society, a society founded several years ago to provide a forum for the born-again