IndraLab

Statements

CHEK2 phosphorylates TP53 on S20. 106 / 109
1 1 1 | 42 52 9
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"20 ATM and ATR directly phosphorylates p53 at Ser15, whereas CHK-2 and CHK-1 phosphorylates Ser20 on p53."
21593792
sparser
"P53 is phosphorylated at S20 by PLK3 and Chk2 following ionizing radiation xref , xref ."
33514736
sparser
"Several studies showed that DNA double-strand breaks induce phosphorylation of p53 S15 by ATM or DNA-PK. xref , xref ATM also activates Chk2, which in turn phosphorylates p53 on S20 which is part of the MDM2 binding site. xref , xref These findings suggested a model that p53 phosphorylation on the N terminus disrupts MDM2 binding and results in p53 stabilization."
20081365
rlimsp
"Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding."
10710310
reach
"Chk2 phosphorylates p53 at Ser 20, inhibiting MDM2-p53 protein binding [XREF_BIBR] but also at several sites located in the C-terminal domain of the p53 protein [XREF_BIBR]."
22420423
sparser
"In addition, following DNA damage, Chk2 and p53 are enriched in PML NBs, where PML promotes Chk2 autophosphorylation, phosphorylation of p53 by Chk2 at Ser20 and subsequent stabilization of p53 ( xref ; xref )."
23316480
rlimsp
"Activated Chk2 subsequently phosphorylated p53 at Ser 20 [39], which upregulated the expression of DNA-damage and cell cycle arrest-related genes (p21 and p27) [40]."
25372714
signor
"The tumour suppressor protein p53 is stabilised and activated in response to ionising radiation. This is known to depend on the kinase atm;recent results suggest atm acts via the downstream kinase chk2/hcds1, which stabilises p53 at least in part by direct phosphorylation of residue serine 20"
10801407
reach
"It is known that DNA damage response (DDR) induced by double strand breaks or uncapped telomeres can result in activation of ATM and Chk2; phosphorylation of p53 by Chk1 or Chk2 at Ser 20 stabilizes p53 by dissociating it from HDM2 and Mdm2 XREF_BIBR, XREF_BIBR."
20526329
sparser
"The serine 20 of p53 is phosphorylated by Chk2, and thereby interrupts the binding of p53 to Mdm2 and interrupts p53 ubiquitination, resulting in greater stability of p53 [ xref ]."
12052256
sparser
"For example, after DNA damage p53 is multiply phosphorylated, with the phosphorylation of Serine 15 by ATM enhancing its transcriptional activity and promoting other phosphorylations,while the ATM-act[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15279785
reach
"In addition, the stabilisation of p53 after IR was normal in the heterozygous LCLs compared to controls (XREF_FIG), an event that is attributed to CHK2 phosphorylation of p53 on Ser20 (Chehab et al, 2000; Shieh et al, 2000)."
15700044
reach
"XREF_BIBR, XREF_BIBR ATM also activates Chk2, which in turn phosphorylates p53 on S20 which is part of the MDM2 binding site."
20081365
reach
"Briefly, the signaling of double stranded (ds) DNA damage to p53 after gamma radiation is mediated by ATM (ataxia-telangiectasia-mutated), which phosphorylates p53 Ser15 and ATM 's downstream effector[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12957542
reach
"Importantly, Chel A induced p53 protein expression was blocked in Chk2-/- cells, and the phosphorylation of p53 at Ser20 and Ser15 were almost abrogated by Chk2 knockout."
24553354
reach
"Indeed, active recombinant MEK1, MEK2 and Chk2 were able to phosphorylate p53 at the Ser20 site."
28038466
sparser
"ATM is also known to phosphorylate Chk2, which subsequently phosphorylates p53 on serine 20 [ xref ]."
23351141
sparser
"Moreover, based on well-documented previous studies [ xref ], phosphorylation of p53 at Ser20 may be also induced by Chk2 in our experimental system."
24553354
reach
"Moreover, Atm also phosphorylates and activates Chk2, which subsequently phosphorylates p53 at Ser 20 in humans (Ser 23 in mouse), stabilizing the p53 protein."
23675047
reach
"CHK2 also phosphorylates P53 Thr18 and Ser20 to promote p21 accumulation and to maintain G2/M arrest."
32518522
reach
"Chk1 and Chk2 phosphorylate p53 at Ser 20, which prevents the efficient recruitment of MDM2."
20950777
reach
"Phosphorylation of p53 at Ser 15 by ATM and at Ser 20 by Chk2 inhibits p53 degradation by MDM2, a RING finger E3 ligase which ubiquitinates and degrades p53 through ubiquitin mediated proteolysis."
20183804
rlimsp
"P53 plays a central role in DNA damage responses and its phosphorylation by Chk2 on Serine 20 is important for its stability and activation [26]."
21625617
reach
"ATM and ATR phosphorylate p53 on Ser15; and CHK1 and CHK2 phosphorylate p53 on Ser20, leading to its accumulation and activation [2-4]."
17118344
sparser
"Meanwhile, Chk2 phosphorylates P53 on Ser 20 , which results in P53 stabilization ( Hirao et al., 2000 )."
23470866
sparser
"Chk2 phosphorylates p53 on S20 ( xref ) (S23 in the mouse) and mice harboring thep53 S23A allele showed an apoptotic phenotype similar to that ofChk2 −/− mice ( xref )."
18614044
rlimsp
"The serine 20 of p53 is phosphorylated by Chk2, and thereby interrupts the binding of p53 to Mdm2 and interrupts p53 ubiquitination, resulting in greater stability of p53 [8]."
12052256
rlimsp
"In non-stressed CML cells, serine 20 of p53 is constitutively phosphorylated by Chk1, and is inhibited by STI571. In response to DNA damage, however, this phosphorylation is mediated by Chk1 and Chk2, and is only partially inhibited by STI571."
15467443
sparser
"A study published in 2000 reported that, upon DNA damage, CHK2 phosphorylates p53 on Ser20 ( xref )."
25404613
sparser
"CHK2 also phosphorylates P53 Thr18 and Ser20 to promote p21 accumulation and to maintain G2/M arrest."
32518522
sparser
"ATM and ATR phosphorylate p53 on Ser15; and CHK1 and CHK2 phosphorylate p53 on Ser20, leading to its accumulation and activation [2–4] ."
17118344
reach
"In contrast to Cdc25A, p53 is phosphorylated not only by Chk1 and Chk2 (on Thr18, Ser20, and possibly other residues) but also directly by the upstream checkpoint kinases ATM and ATR, particularly, on[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15279786
sparser
"ATM activates downstream kinases Chk1 and Chk2, which then phosphorylate p53 at Ser20."
16893723
sparser
"For instance, the DNA damage insult mediates phosphorylation of p53 at Ser15 and Ser20 by ATM, ATR, DNA-PK, Chk1, and Chk2, resulting in an increase of transcriptional activity of p53 [ xref , xref , xref ]."
32660118
reach
"CHEK2 can promote the phosphorylation of tumor suppressor gene p53 (Ser20), block the binding of murine double micro-2 (MDM2) protein to p53 and its role in degradation of p53, thus improving the stability of p53 in cells [XREF_BIBR]."
29761796
sparser
"It is important to note that the Chk2-induced p53 phosphorylation at Ser20 and ATM-driven p53 phosphorylation at position Ser15 stabilize p53 and promote accumulation of activated p53 in the nucleus xref ."
24358900
sparser
"PPM1D dephosphorylates and inhibits several p53 activating kinases, including p38 MAP kinase, which phosphorylates p53 at serines 33 and 46, ATM, which phosphorylates p53 at serine 15, and Chk1 and Chk2, which phosphorylate p53 at serine 20 (Fujimoto et al., 2006, Lu et al., 2005, Oliva-Trastoy et al., 2006,Shreeram et al., 2006, Takekawa et al., 2000 and Yoda et al., 2006)."
25823026
reach
"A study published in 2000 reported that, upon DNA damage, CHK2 phosphorylates p53 on Ser20."
25404613
sparser
"Thus, a pathway emerges in which DNA damage leads to ATM-dependent activation of Chk2, which phosphorylates p53 on Ser20 to inhibit its association with Mdm2, stabilizing p53."
11063934
sparser
"CHK2 phosphorylates tumor inhibitor p53 at the ser15 and ser20 residues, leading to its stabilization and activation, finally resulting in cell cycle arrest (Ou et al., xref )."
36177479
sparser
"Chk1 and Chk2 phosphorylate p53 at Ser 20, which prevents the efficient recruitment of MDM2."
20950777
phosphoelm
No evidence text available
17339337
reach
"Chk2 phosphorylates p53 on S20 (Chehab et al., 2000) (S23 in the mouse), and mice harboring the p53 S23A allele showed an apoptotic phenotype similar to that of Chk2 -/- mice (MacPherson et al., 2004)[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18614044
sparser
"It is known that DNA damage response (DDR) induced by double strand breaks or uncapped telomeres can result in activation of ATM and Chk2; phosphorylation of p53 by Chk1 or Chk2 at Ser-20 stabilizes p53 by dissociating it from HDM2/Mdm2 xref , xref ."
20526329
sparser
"In addition, the stabilisation of p53 after IR was normal in the heterozygous LCLs compared to controls ( xref ), an event that is attributed to CHK2 phosphorylation of p53 on Ser20 ( xref ; xref )."
15700044
reach
"Thus, a pathway emerges in which DNA damage leads to ATM dependent activation of Chk2, which phosphorylates p53 on Ser20 to inhibit its association with Mdm2, stabilizing p53.Genetic evidence lends su[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11063934
sparser
"ATM phosphorylates p53 at serine 15 xref , xref , whereas Chk2 phosphorylates p53 at serine 20 in response to activation by ATM xref , xref ."
19544417
sparser
"ATM indirectly regulates MDM2-mediated degradation of p53 through phosphorylation of Chk2 which then phosphorylates p53 at Ser-20 to prevent the formation of the MDM2–p53 complex (Dumaz et al., xref )."
22649771
sparser
"The observation that both ATM kinase dependent p53-serine 15, and ATM and Chk2 dependent p53-serine 20 phosphorylation are maximal two hours following irradiation, prior to maximal p53 protein level four hours after irradiation, is consistent with a function of these two kinases in p53 stabilization and activation."
19544417
reach
"ATM, ATR, and DNA-PK phosphorylate p53 on S15, while CHK1 and CHK2 phosphorylate p53 on S20 which stabilize p53 by preventing binding to Mdm2 [XREF_BIBR - XREF_BIBR]."
20860841
sparser
"Phosphorylation of TP53 at serine-20 by CHK2 prevents MDM2-mediated TP53 degradation."
23144912
sparser
"WIP1 also dephosphorylates and inactivates the p53-activating kinases ATM, CHK1 and CHK2, which phosphorylate p53 at Ser15 and Ser20, respectively [ xref , xref , xref , xref , xref ]."
| PMC
reach
"N-terminal phosphorylation of p53 at serine residues S15 and S20 by ATM, ATR, CHK1 and CHK2, and other kinases stabilizes and activates p53 [XREF_BIBR, XREF_BIBR]."
29963241
sparser
"The activated ATM/ATR phosphorylate p53 at Ser15 in humans, Ser18 in mouse, Chk1 and Chk2, which further phosphorylate p53 at Ser20. xref , xref Phosphorylation at residue Ser18 in mouse p53 does not contribute to the stability of p53, but it rather stimulates its transcriptional activity. xref p53 plays a central role in cell cycle arrest upon DNA damage."
19923893
reach
"CHK2 acts on p53 in a similar fashion and phosphorylates p53 at S20, contributing to p53 dependent cell cycle arrest in the G1 phase [XREF_BIBR]."
33322746
sparser
"Chk2 phosphorylates p53 on S20 () (S23 in the mouse), and mice harboring the allele showed an apoptotic phenotype similar to that of mice ()."
18614044
sparser
"This group has demonstrated that Chk2 is able to phosphorylate p53 on serine 20, and that this phosphorylation event triggers dissociation of preformed complexes between p53 and MDM2 under conditions[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10801407
reach
"Meanwhile, Chk2 phosphorylates P53 on Ser 20, which results in P53 stabilization (Hirao et al., 2000)."
23470866
reach
"Both Chk1 and Chk2 can phosphorylate p53 on several sites including S20 (S23 in mice) [XREF_BIBR]."
19473886
reach
"The tumor suppressor gene p53 is a key target of Chk2 in DNA damage response and Chk2 can phosphorylate p53 on Ser 20 and dissociate p53 from Mdm2 to maintain its stabilization and accumulation after DNA damage XREF_BIBR, XREF_BIBR."
29805302
sparser
"Phosphorylation of p53 on serine-20 by Chk2 and Chk1 stabilizes the protein as well ( xref , xref )."
28140789
sparser
"ATM-activated Chk2 kinase also phosphorylates p53 at the threonine-18 and serine-20 residues [ xref , xref ]."
34440406
sparser
"Recent data [45–47] show that activated Chk2 and Chk1 phosphorylate p53 on serine 20, an event which leads to decreased protein turnover and thus accumulation of p53 ( Fig. 2 [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11223026
sparser
"Since S20 in p53 is not only phosphorylated by Chk2, but also by other protein kinases such as MAPKAPK2, JNK and PLK3 kinase one could speculate that one of these kinases is responsible for the obser[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18812180
rlimsp
"In addition, phosphorylation of p53 at Ser20 by Chk2 (58) does not participate either (Figure 5) consistent with the lack of effect of Chk2 or Chk1 on p53-RPA interaction (Figure S3)."
22797063
rlimsp
"Although Chk2 activated by cis-Pt has been reported to phosphorylate Ser20 [33] and its knock-down in A2780 cells reduces the ability of cis-Pt to induce p21 in a p53-dependent manner [35], MEK1/2 has not been associated previously with phosphorylation at Ser20."
28038466
reach
"In turn, CHK2 and CHK1 phosphorylate p53 at Ser20, thereby activating it."
23892398
reach
"Active CHK2 phosphorylates Ser20 on p53, inhibiting the p53 and MDM2 interaction and stabilizing p53."
23843721
sparser
"Chk2 phosphorylates p53 at Ser 20, inhibiting MDM2-p53 protein binding [ xref ] but also at several sites located in the C-terminal domain of the p53 protein [ xref ]."
22420423
rlimsp
"While Chk2 phosphorylates p53 at Ser 20, thereby stabilizing p53 by preventing MDM2 binding [19], Chk2 also phosphorylates p53 at six additional sites, including Ser 313 and Ser 314 located in the nuclear localization signal domain of p53 [51]."
18725978
reach
"For example, p53 is phosphorylated at Ser20 by the checkpoint kinase Chk2 after IR, which results in p53 's dissociation from Mdm2 and its subsequent stabilization."
20096447
sparser
"However, upon transfection with wildtype Chk2 (lane 7) but also in the case of the two mutants replacing T68 by either alanine (lane 8) or by aspartic acid (lane 9) phosphorylation of S20 is observed,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18812180
sparser
"Chk2 also phosphorylates the transcription factor p53 on Ser20 and stabilizes p53, and consequently causes G1 arrest [6] ."
11728459
sparser
"In addition, phosphorylation of p53 at Ser20 by Chk2 ( xref ) does not participate either ( xref ) consistent with the lack of effect of Chk2 or Chk1 on p53-RPA interaction ( xref )."
22797063
sparser
"Chk2 phosphorylates p53 at serine 20 and interferes with the p53-Mdm2 interaction serving to stabilize p53 (see above)."
20651945
reach
"In addition, following DNA damage, Chk2 and p53 are enriched in PML NBs, where PML promotes Chk2 autophosphorylation, phosphorylation of p53 by Chk2 at Ser20 and subsequent stabilization of p53."
23316480
sparser
"Subsequently, activated Chk2 phosphorylates p53 on Ser20 to reduce the interaction of p53 with MDM2 ( xref )."
30534074
reach
"Both Chk1 and Chk2 phosphorylate p53 at Ser 20, which prevents the efficient recruitment of MDM2."
21197464
reach
"As discussed previously, Chk2 phosphorylates p53 in vitro on Ser20 [27,28] and dissociates Mdm2 from p53 [27]."
11063934
sparser
"ATM also phosphorylates CHK2, which can in turn phosphorylate p53 at serine 20 [ xref , xref ]."
32257107
sparser
"In addition, the ATM-dependent chk2 protein phosphorylates p53 at serine-20."
11173129
reach
"These data suggested that p-Chk2 played an important role on the reversal effect of oroxylin A in MCF7 and ADR cells.In this study, we revealed that oroxylin A arrested Adriamycin resistant human brea[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23470866
reach
"ATM activates downstream kinases Chk1 and Chk2, which then phosphorylate p53 at Ser20."
16893723
sparser
"ATM, ATR, and DNA-PKcs phosphorylate p53 at Ser15, whereas the ATM/ATR substrates CHK1 and CHK2 phosphorylate p53 at Ser20 ( xref A) [ xref ]."
33924934
reach
"The N-terminal activation domain of p53 does not contain the classical Chk1 and Chk2 consensus target sequence found in other substrates such as the Cdc25 phosphatases, and the physiological tetrameri[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
15279786
sparser
"Chk2 can also phosphorylate p53-Ser20 to induce stabilization of the p53 protein following radiation ( xref )."
25174607
reach
"Activated Chk2 subsequently phosphorylated p53 at Ser 20 XREF_BIBR, which upregulated the expression of DNA-damage and cell cycle arrest related genes (p21 and p27) XREF_BIBR."
25372714
reach
"Chk2 also phosphorylates the transcription factor p53 on Ser20 and stabilizes p53, and consequently causes G1 arrest [6]."
11728459
reach
"After DNA damage, ATM and CHK2 phosphorylate p53 (S15 and S20), thus reducing its ability to bind MDM2 and contributing to its stabilization [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
25247188
reach
"Others reported that ATM activates checkpoint kinase 2 (Chk2), which phosphorylates P53 on Ser20 residue."
34072430
sparser
"As discussed previously, Chk2 phosphorylates p53 in vitro on Ser20 [27 ,28 ] and dissociates Mdm2 from p53 [27 ] ."
11063934
sparser
"Phosphorylation of p53 on Serine-20 by CHK2 leads to a reduction in binding affinity of the E3 ubiquitin ligase MDM2 to p53, leading to an increase in p53 levels."
33855023
biopax:phosphositeplus
No evidence text available
sparser
"The tumor suppressor gene p53 is a key target of Chk2 in DNA damage response and Chk2 can phosphorylate p53 on Ser-20 and dissociate p53 from Mdm2 to maintain its stabilization and accumulation after DNA damage xref , xref ."
29805302
rlimsp
"Chk2 phosphorylates p53 at Ser 20, inhibiting MDM2-p53 protein binding [16] but also at several sites located in the C-terminal domain of the p53 protein [17]."
22420423
reach
"Moreover, based on well documented previous studies [XREF_BIBR], phosphorylation of p53 at Ser20 may be also induced by Chk2 in our experimental system."
24553354
sparser
"Active CHK2 phosphorylates Ser20 on p53, inhibiting the p53/MDM2 interaction and stabilizing p53."
23843721
sparser
"ATM also activates CHK2, a serine threonine kinase, which phosphorylates p53 at threonine 18 and serine 20."
22778557
sparser
"Indeed, active recombinant MEK1, MEK2 and Chk2 were able to phosphorylate p53 at the Ser20 site (Figure xref )."
28038466
reach
"After DNA damage, ATM and CHK2 phosphorylate p53 (S15 and S20), thus reducing its ability to bind MDM2 and contributing to its stabilization [XREF_BIBR, XREF_BIBR]."
27258263
sparser
"Additionally, ATM/ATR-activated Chk1 and Chk2 kinases phosphorylate the p53 transactivation domain on serine 20, thereby stimulating p53 activity (Dornan et al., xref )."
22891162
sparser
"For example, p53 is phosphorylated at Ser20 by the checkpoint kinase Chk2 after IR, which results in p53's dissociation from Mdm2 and its subsequent stabilization ( xref ; xref ; xref )."
20096447
reach
"While Chk2 phosphorylates p53 at Ser 20, thereby stabilizing p53 by preventing MDM2 binding XREF_BIBR, Chk2 also phosphorylates p53 at six additional sites, including Ser 313 and Ser 314 located in the nuclear localization signal domain of p53 XREF_BIBR."
18725978
reach
"Expression of a dominant negative allele of Chk2 prevents both stabilization of p53 and Ser20 phosphorylation upon treatment with ionizing radiation or UV light [27]."
11063934
sparser
"Recent studies have demonstrated that Ser 20 on p53 is phosphorylated by Chk1 (checkpoint kinase 1) or Chk2, enhancing its tetramerization, stability, and activity in response to DNA damage [ xref ]."
18778462
reach
"Chk2 phosphorylates p53 on S20 (S23 in the mouse) and mice harboring the p53 S23A allele showed an apoptotic phenotype similar to that of Chk2 -/- mice."
18614044