ERKs and p38 Kinase Phosphorylate p53 Protein at Serine 15 in Response to UV Radiation

She, Qing‐Bai; Chen, Nanyue; Dong, Zigang

doi:10.1074/jbc.m001020200

Cited by 319 publications

(286 citation statements)

References 53 publications

(75 reference statements)

Supporting

Mentioning

266

Contrasting

Unclassified

Order By: Relevance

“…JNK, another MAPK family member, only phosphorylates p53 on Ser20 upon UV radiation [17]. Although Ser15 was reported to be phosphorylated by p38 and ERK simultaneously [6], our study showed that HUV and LUV-induced Ser15 phosphorylation was mediated by p38 and ERK, respectively. This suggests that p53-mediated determination of cell fate is regulated by different upstream kinases.…”

Section: Discussioncontrasting

confidence: 52%

“…2A and B, p38 was only co-precipitated by p53 with HUV radiation. Although there already existed reports regarding UV-induced interaction between p38 and p53 [6,8], our results clarified that this interaction was only induced by HUV, but not LUV radiation. …”

Section: Dose-dependent Interaction Between P38 and P53 Induced By Uvcontrasting

confidence: 61%

“…Upon UV radiation, p38 phosphorylates p53 on at least four sites (Ser15, Ser33, Ser46, and Ser392), leading to its escape from Mdm2-dependent degradation [6,8,12,17,25]. However, among all the phosphorylation sites we detected, including Ser6, Ser9, Ser15, Ser20, Ser37, Ser46, and Ser392 (Fig.…”

Section: Discussionmentioning

confidence: 81%

“…HUV and LUV-induced phosphorylation of p53 on Ser15, a widely reported phosphorylation site of p53 by p38 upon UV radiation [6,17], were different. Surprisingly, LUV induced a higher level of phosphorylation on p53 Ser15 than HUV (Fig.…”

Section: Uv-induced P53 Phosphorylation On Ser15 By P38 Is Dosedependentmentioning

confidence: 83%

“…p38 MAPK, one of the four MAPK subfamilies in mammalian cells, is activated by proinflammatory cytokines and environmental stresses [4][5][6]. p38 is not only reported to be phosphorylated and activated to mediate cell apoptosis [7][8][9], but also to have cell protective effects under certain circumstances [10,11].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

UV‐induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate

Gong¹,

Liu²,

Xin³

et al. 2010

FEBS Letters

View full text Add to dashboard Cite

Edited by Varda RotterKeywords: p38 mitogen-activated protein kinase p53 DNA damage Cell apoptosis Cell survival a b s t r a c t p53 plays a fundamental role in the maintenance of genome integrity after DNA damage, deciding whether cells repair and live, or die. However, the rules that govern its choice are largely undiscovered. Here we show that the functional relationship between p38 and p53 is crucial in defining the cell fate after DNA damage. Upon low dose ultraviolet (UV) radiation, p38 and p53 protect the cells from apoptosis separately. Conversely, they function together to favor apoptosis upon high dose UV exposure. Taken together, a UV-induced, dose-dependent interaction between p38 and p53 acts as a switch to determine cell fate. Structured summary:MINT-8050838: p53 (uniprotkb:P02340) physically interacts (MI:0915) with p38 (uniprotkb:P47811) by anti bait coimmunoprecipitation (MI:0006) MINT-8050948: p53 (uniprotkb:P04637) physically interacts (MI:0915) with p38 (uniprotkb:P47811) by anti tag coimmunoprecipitation (MI:0007)

show abstract

Section: Discussioncontrasting

confidence: 52%

Section: Dose-dependent Interaction Between P38 and P53 Induced By Uvcontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 81%

Section: Uv-induced P53 Phosphorylation On Ser15 By P38 Is Dosedependentmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

UV‐induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate

Gong¹,

Liu²,

Xin³

et al. 2010

FEBS Letters

View full text Add to dashboard Cite

show abstract

Methotrexate increases expression of cell cycle checkpoint genes via JNK activation

Spurlock

Tossberg²,

Fuchs

et al. 2012

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective To assess defects in expression of critical cell cycle checkpoint genes and proteins in subjects with rheumatoid arthritis relative to presence or absence of methotrexate medication and assess the role of Jun N-terminal kinase in methotrexate induction of these genes. Methods Flow cytometry analysis was used to quantify changes in intracellular proteins, measure reactive oxygen species (ROS), and determine apoptosis in different lymphoid populations. Quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) was employed to determine changes in cell cycle checkpoint target genes. Results RA subjects express lower baseline levels of MAPK9, TP53, CDKN1A, CDKN1B, CHEK2, and RANGAP1 messenger RNA (mRNA) and total JNK protein. MAPK9, TP53, CDKN1A, and CDKN1B mRNA expression, but not CHEK2, and RANGAP1, is higher in patients on low-dose MTX therapy. Further, JNK levels inversely correlate with CRP levels in RA patients. In tissue culture, MTX induces expression of both p53 and p21 by JNK2 and JNK1-dependent mechanisms, respectively, while CHEK2 and RANGAP1 are not induced by MTX. MTX also induces ROS production, JNK activation, and sensitivity to apoptosis in activated T cells. Supplementation with tetrahydrobiopterin blocks these MTX-mediated effects. Conclusions Our findings support the notion that MTX restores some, but not all of the proteins contributing to cell cycle checkpoint deficiencies in RA T cells by a JNK dependent pathway.

show abstract

Effect of alteration of caveolin‐1 expression on doxorubicin‐induced apoptosis in H9c2 cardiac cells

Takaguri

Kamato

Satoh

et al. 2015

Cell Biology International

View full text Add to dashboard Cite

Doxorubicin is an anthracycline antibiotic widely used in cancer treatment. Although its antitumor efficacy appears to be dose dependent, its clinical use is greatly restricted by the development of cardiotoxicity associated with apoptosis. Although caveolin-1, the major structural protein in caveolae, can positively or negatively regulate apoptosis depending on the stimulus or cell types, the contribution of caveolin-1 to doxorubicin-induced apoptosis remains unknown. This study was performed to identify the regulatory role of caveolin-1 on doxorubicin-induced apoptosis in H9c2 cardiac cells using a genetic approach. Caveolin-1 knockdown with a short hairpin (sh) RNA adenovirus, but not overexpression of wild-type caveolin-1, resulted in a marked inhibition of doxorubicin-induced caspase-3 cleavage. However, caveolin-1 knockdown tended to protect against doxorubicin-induced decrease in cell viability, but it did not significantly reverse cell death induced by doxorubicin. Doxorubicin stimulated the phosphorylation of p38 and extracellular signal regulated kinase (ERK). Doxorubicin-induced caspase-3 cleavage was inhibited by U0126, a MEK inhibitor or SB203580, a p38 inhibitor. Caveolin-1 knockdown markedly inhibited doxorubicin-induced p-38 phosphorylation but not ERK-mediated p-53 phosphorylation in H9c2 cardiac cells. Our results suggest that reduced caveolin-1 expression plays an anti-apoptotic role in doxorubicin-induced apoptosis but that it is insufficient to prevent such an apoptosis in H9c2 cardiac cells.

show abstract

ERKs and p38 Kinase Phosphorylate p53 Protein at Serine 15 in Response to UV Radiation

Cited by 319 publications

References 53 publications

UV‐induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate

UV‐induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate

Methotrexate increases expression of cell cycle checkpoint genes via JNK activation

Effect of alteration of caveolin‐1 expression on doxorubicin‐induced apoptosis in H9c2 cardiac cells

Contact Info

Product

Resources

About