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PMID |
Sentence |
1 |
15007383
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Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases.
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2 |
15007383
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Nore1, a noncatalytic protein identified by its ability to bind selectively to active Ras, is most closely related in amino-acid sequence to the tumor suppressor RASSF1.
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3 |
15007383
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Both are expressed predominantly as a longer (Nore1A/RASSF1A) and/or shorter (Nore1B/RASSF1C) polypeptide; all four polypeptides contain a Ras-association domain and bind, through their conserved carboxytermini, the proapoptotic protein kinases MST1 and MST2.
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4 |
15007383
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Moreover, the expression of the longer polypeptide is downregulated in human tumor cell lines through promoter methylation (frequently for RASSF1A, less regularly for Nore1A).
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5 |
15007383
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The expression of Nore1A or Nore1B suppresses colony formation by the A549 and G361 lines, as effectively in A549 as does RASSF1A; colony formation in the NCI-H460 and M14 lines is unaffected.
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6 |
15007383
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Thus, Nore1 suppresses the growth of some tumor cell lines through as yet unidentified effectors, independent of Ras-like proteins or MST1/2.
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7 |
15109305
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Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.
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8 |
15109305
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MST1 (mammalian Sterile20-like 1) and MST2 are closely related Class II GC (protein Ser/Thr) kinases that initiate apoptosis when transiently overexpressed in mammalian cells.
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9 |
15109305
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In the present study, we show that recombinant MST1/2 undergo a robust autoactivation in vitro, mediated by an intramolecular autophosphorylation of a single site [MST1(Thr183)/MST2(Thr180)] on the activation loop of an MST dimer.
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10 |
15109305
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Endogenous MST1 immunoprecipitated from KB cells is specifically associated with substoichiometric amounts of the growth inhibitory polypeptides RASSF1A and NORE1A (novel Ras effector 1A; a Ras-GTP-binding protein).
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11 |
15109305
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Co-expression of RASSF1A, RASSF1C, NORE1A and NORE1B with MST1 markedly suppresses MST1(Thr183) phosphorylation in vivo and abolishes the ability of MST1 to undergo Mg-ATP-mediated autoactivation in vitro; direct addition of purified NORE1A in vitro also inhibits MST1 activation.
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12 |
15109305
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In contrast, co-transfection of MST1 with NORE1A modified by the addition of a C-terminal CAAX motif results in a substantial increase in MST1(Thr183) phosphorylation, as does fusion of a myristoylation motif directly on to the MST1 N-terminus.
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13 |
15109305
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Moreover, MST1 polypeptides, bound via wild-type NORE1A to Ras(G12V) (where G12V stands for Gly12Val), exhibit higher Thr183 phosphorylation compared with MST1 bound to NORE1A alone.
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14 |
15109305
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Nevertheless, serum stimulation of KB cells does not detectably increase the activation state of endogenous MST1 or MST2 despite promoting the recruitment of the endogenous NORE1-MST1 complex to endogenous Ras.
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15 |
15109305
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We propose that the NORE1/RASSF1 polypeptides, in addition to their role in maintaining the low activity of MST1 in vivo, direct MST1 to sites of activation and perhaps co-localization with endogenous substrates.
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16 |
15109305
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Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.
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17 |
15109305
|
MST1 (mammalian Sterile20-like 1) and MST2 are closely related Class II GC (protein Ser/Thr) kinases that initiate apoptosis when transiently overexpressed in mammalian cells.
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18 |
15109305
|
In the present study, we show that recombinant MST1/2 undergo a robust autoactivation in vitro, mediated by an intramolecular autophosphorylation of a single site [MST1(Thr183)/MST2(Thr180)] on the activation loop of an MST dimer.
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19 |
15109305
|
Endogenous MST1 immunoprecipitated from KB cells is specifically associated with substoichiometric amounts of the growth inhibitory polypeptides RASSF1A and NORE1A (novel Ras effector 1A; a Ras-GTP-binding protein).
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20 |
15109305
|
Co-expression of RASSF1A, RASSF1C, NORE1A and NORE1B with MST1 markedly suppresses MST1(Thr183) phosphorylation in vivo and abolishes the ability of MST1 to undergo Mg-ATP-mediated autoactivation in vitro; direct addition of purified NORE1A in vitro also inhibits MST1 activation.
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21 |
15109305
|
In contrast, co-transfection of MST1 with NORE1A modified by the addition of a C-terminal CAAX motif results in a substantial increase in MST1(Thr183) phosphorylation, as does fusion of a myristoylation motif directly on to the MST1 N-terminus.
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22 |
15109305
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Moreover, MST1 polypeptides, bound via wild-type NORE1A to Ras(G12V) (where G12V stands for Gly12Val), exhibit higher Thr183 phosphorylation compared with MST1 bound to NORE1A alone.
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23 |
15109305
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Nevertheless, serum stimulation of KB cells does not detectably increase the activation state of endogenous MST1 or MST2 despite promoting the recruitment of the endogenous NORE1-MST1 complex to endogenous Ras.
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24 |
15109305
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We propose that the NORE1/RASSF1 polypeptides, in addition to their role in maintaining the low activity of MST1 in vivo, direct MST1 to sites of activation and perhaps co-localization with endogenous substrates.
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25 |
15109305
|
Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras.
|
26 |
15109305
|
MST1 (mammalian Sterile20-like 1) and MST2 are closely related Class II GC (protein Ser/Thr) kinases that initiate apoptosis when transiently overexpressed in mammalian cells.
|
27 |
15109305
|
In the present study, we show that recombinant MST1/2 undergo a robust autoactivation in vitro, mediated by an intramolecular autophosphorylation of a single site [MST1(Thr183)/MST2(Thr180)] on the activation loop of an MST dimer.
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28 |
15109305
|
Endogenous MST1 immunoprecipitated from KB cells is specifically associated with substoichiometric amounts of the growth inhibitory polypeptides RASSF1A and NORE1A (novel Ras effector 1A; a Ras-GTP-binding protein).
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29 |
15109305
|
Co-expression of RASSF1A, RASSF1C, NORE1A and NORE1B with MST1 markedly suppresses MST1(Thr183) phosphorylation in vivo and abolishes the ability of MST1 to undergo Mg-ATP-mediated autoactivation in vitro; direct addition of purified NORE1A in vitro also inhibits MST1 activation.
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30 |
15109305
|
In contrast, co-transfection of MST1 with NORE1A modified by the addition of a C-terminal CAAX motif results in a substantial increase in MST1(Thr183) phosphorylation, as does fusion of a myristoylation motif directly on to the MST1 N-terminus.
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31 |
15109305
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Moreover, MST1 polypeptides, bound via wild-type NORE1A to Ras(G12V) (where G12V stands for Gly12Val), exhibit higher Thr183 phosphorylation compared with MST1 bound to NORE1A alone.
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32 |
15109305
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Nevertheless, serum stimulation of KB cells does not detectably increase the activation state of endogenous MST1 or MST2 despite promoting the recruitment of the endogenous NORE1-MST1 complex to endogenous Ras.
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33 |
15109305
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We propose that the NORE1/RASSF1 polypeptides, in addition to their role in maintaining the low activity of MST1 in vivo, direct MST1 to sites of activation and perhaps co-localization with endogenous substrates.
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34 |
16757333
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Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases.
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35 |
16757333
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The expression of the RASSF1A and Nore1A isoforms is extinguished selectively by gene loss and/or epigenetic mechanisms in a considerable fraction of epithelial cancers and cell lines derived therefrom, and reexpression usually suppresses the proliferation and tumorigenicity of these cells.
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36 |
16757333
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RASSF1A/Nore1A can cause cell cycle delay in G1 and/or M and may promote apoptosis.
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37 |
16757333
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The founding member, Nore1A, binds preferentially through its RA domain to the GTP-charged forms of Ras, Rap-1, and several other Ras subfamily GTPases with high affinity.
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38 |
16757333
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By contrast, RASSF1, despite an RA domain 50% identical to Nore1, exhibits relatively low affinity for Ras-like GTPases but may associate with Ras-GTP indirectly.
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39 |
16757333
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Each of the RASSF polypeptides, including the C. elegans ortholog encoded by T24F1.3, binds to the Ste20-related protein kinases MST1 and MST2 through the SARAH domains of each partner.
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40 |
16757333
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The recombinant MST1/2 kinases, spontaneous dimers, autoactivate in vitro through an intradimer transphosphorylation of the activation loop, and the Nore1/RASSF1 polypeptides inhibit this process.
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41 |
16757333
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Recombinant MST1 is strongly activated in vivo by recruitment to the membrane; the recombinant MST1 that is bound to RasG12V through Nore1A is activated; however, the bulk of MST1 is not.
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42 |
16757333
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Endogenous complexes of MST1 with both Nore1A and RASSF1A are detectable, and Nore1A/MST1 can associate with endogenous Ras in response to serum addition.
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43 |
16757333
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Nevertheless, the physiological functions of the Nore1/RASSF polypeptides in mammalian cells, as well as the role of the MST1/2 kinases in their growth-suppressive actions, remain to be established.
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44 |
16757333
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Overexpression of mammalian MST1 or MST2 promotes apoptosis, as does overexpression of mutant active Ki-Ras.
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45 |
16757333
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Interference with the ability of endogenous MST1/2 to associate with the Nore1/RASSF polypeptides inhibits Ras-induced apoptosis.
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46 |
16757333
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Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases.
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47 |
16757333
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The expression of the RASSF1A and Nore1A isoforms is extinguished selectively by gene loss and/or epigenetic mechanisms in a considerable fraction of epithelial cancers and cell lines derived therefrom, and reexpression usually suppresses the proliferation and tumorigenicity of these cells.
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48 |
16757333
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RASSF1A/Nore1A can cause cell cycle delay in G1 and/or M and may promote apoptosis.
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49 |
16757333
|
The founding member, Nore1A, binds preferentially through its RA domain to the GTP-charged forms of Ras, Rap-1, and several other Ras subfamily GTPases with high affinity.
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50 |
16757333
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By contrast, RASSF1, despite an RA domain 50% identical to Nore1, exhibits relatively low affinity for Ras-like GTPases but may associate with Ras-GTP indirectly.
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51 |
16757333
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Each of the RASSF polypeptides, including the C. elegans ortholog encoded by T24F1.3, binds to the Ste20-related protein kinases MST1 and MST2 through the SARAH domains of each partner.
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52 |
16757333
|
The recombinant MST1/2 kinases, spontaneous dimers, autoactivate in vitro through an intradimer transphosphorylation of the activation loop, and the Nore1/RASSF1 polypeptides inhibit this process.
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53 |
16757333
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Recombinant MST1 is strongly activated in vivo by recruitment to the membrane; the recombinant MST1 that is bound to RasG12V through Nore1A is activated; however, the bulk of MST1 is not.
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54 |
16757333
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Endogenous complexes of MST1 with both Nore1A and RASSF1A are detectable, and Nore1A/MST1 can associate with endogenous Ras in response to serum addition.
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55 |
16757333
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Nevertheless, the physiological functions of the Nore1/RASSF polypeptides in mammalian cells, as well as the role of the MST1/2 kinases in their growth-suppressive actions, remain to be established.
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56 |
16757333
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Overexpression of mammalian MST1 or MST2 promotes apoptosis, as does overexpression of mutant active Ki-Ras.
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57 |
16757333
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Interference with the ability of endogenous MST1/2 to associate with the Nore1/RASSF polypeptides inhibits Ras-induced apoptosis.
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58 |
18328708
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MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation.
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