Ser367
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Home > Phosphorylation Site Page: > Ser367  -  MDM4 (human)

Site Information
PDCRRtIsAPVVRPk   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 457676

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 22 ) , immunoassay ( 22 ) , immunoprecipitation ( 2 , 4 , 11 , 17 , 19 , 20 , 22 ) , mass spectrometry ( 1 , 3 , 5 , 7 , 10 , 12 , 14 , 15 , 22 , 24 ) , mass spectrometry (in vitro) ( 6 ) , mutation of modification site ( 6 , 9 , 11 , 13 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ) , peptide sequencing ( 24 ) , phospho-antibody ( 2 , 4 , 9 , 11 , 19 , 20 , 21 , 22 , 23 , 24 ) , phosphopeptide mapping ( 22 ) , western blotting ( 2 , 4 , 6 , 9 , 11 , 13 , 17 , 18 , 22 , 24 )
Disease tissue studied:
bone cancer ( 2 , 4 , 9 , 11 , 13 , 16 , 17 , 22 , 24 ) , breast cancer ( 4 , 5 , 12 , 22 , 24 ) , breast ductal carcinoma ( 5 ) , HER2 positive breast cancer ( 3 ) , luminal A breast cancer ( 3 ) , luminal B breast cancer ( 3 ) , breast cancer, surrounding tissue ( 3 ) , breast cancer, triple negative ( 3 ) , colorectal cancer ( 11 , 22 , 24 ) , colorectal carcinoma ( 11 , 22 , 24 ) , lung cancer ( 4 , 6 , 11 , 12 , 13 , 17 , 22 ) , non-small cell lung cancer ( 4 , 6 , 11 , 12 , 13 , 17 , 22 ) , non-small cell lung adenocarcinoma ( 4 ) , neuroblastoma ( 17 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
CK1A (human) ( 2 ) , PPM1D (human) ( 16 )
Putative in vivo kinases:
Akt1 (human) ( 19 ) , Chk1 (human) ( 21 ) , Chk2 (human) ( 11 , 20 , 22 , 24 )
Kinases, in vitro:
Akt1 (human) ( 19 ) , Chk1 (human) ( 21 , 24 ) , Chk2 (human) ( 20 , 24 )
Putative upstream phosphatases:
PPP1CA (human) ( 9 ) , PPP1CB (human) ( 9 ) , PPP1CC (human) ( 9 )
Phosphatases, in vitro:
PPP1CA (human) ( 9 ) , PPP1CB (human) ( 9 ) , PPP1CC (human) ( 9 )
Treatments:
adriamycin ( 19 ) , Chk2_inhibitor_II ( 20 ) , ionizing_radiation ( 11 , 22 ) , KU-55933 ( 20 ) , MG132 ( 19 ) , neocarzinostatin ( 9 , 20 ) , siRNA ( 9 ) , UCN-01 ( 21 ) , UV ( 21 , 22 )

Downstream Regulation
Effects of modification on MDM4:
intracellular localization ( 17 , 20 , 21 , 22 ) , molecular association, regulation ( 4 , 6 , 11 , 16 , 17 , 19 , 20 , 21 , 22 , 23 ) , phosphorylation ( 11 ) , protein degradation ( 9 , 11 , 13 , 16 , 20 , 22 , 23 , 24 , 25 ) , protein stabilization ( 19 ) , ubiquitination ( 11 , 13 , 16 , 17 , 22 )
Effects of modification on biological processes:
cell growth, altered ( 23 ) , transcription, induced ( 9 , 11 ) , transcription, inhibited ( 22 )
Induce interaction with:
14-3-3 beta (human) ( 19 , 22 ) , 14-3-3 epsilon (human) ( 23 ) , 14-3-3 gamma (human) ( 6 , 21 ) , 14-3-3 theta (human) ( 20 ) , 14-3-3 zeta (human) ( 19 ) , MDM2 (human) ( 11 , 16 )
Inhibit interaction with:
CK1A (human) ( 11 ) , MDM2 (human) ( 17 ) , USP7 (human) ( 16 ) , p53 (human) ( 11 , 17 )

References 

1

Bouhaddou M, et al. (2020) The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell
32645325   Curated Info

2

Liu X, et al. (2019) Tumor-derived CK1α mutations enhance MDMX inhibition of p53. Oncogene
31462704   Curated Info

3

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

4

Wei X, et al. (2016) Secondary interaction between MDMX and p53 core domain inhibits p53 DNA binding. Proc Natl Acad Sci U S A 113, E2558-63
27114532   Curated Info

5

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
24719451   Curated Info

6

He G, et al. (2014) AMP-Activated Protein Kinase Induces p53 by Phosphorylating MDMX and Inhibiting Its Activity. Mol Cell Biol 34, 148-57
24190973   Curated Info

7

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
23749302   Curated Info

8

Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21
23312004   Curated Info

9

Lu Z, et al. (2013) Protein phosphatase 1 inhibits p53 signaling by dephosphorylating and stabilizing Mdmx. Cell Signal 25, 796-804
23277204   Curated Info

10

Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71
23186163   Curated Info

11

Wu S, et al. (2012) Casein Kinase 1α Regulates an MDMX Intramolecular Interaction To Stimulate p53 Binding. Mol Cell Biol 32, 4821-32
23028042   Curated Info

12

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
22617229   Curated Info

13

Li X, et al. (2012) Abnormal MDMX degradation in tumor cells due to ARF deficiency. Oncogene 31, 3721-32
22120712   Curated Info

14

Guo A (2011) CST Curation Set: 11984; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]XP
Curated Info

15

Guo A (2011) CST Curation Set: 11989; Year: 2011; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]XP Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser) 14-3-3 Binding Motif Antibody Cat#: 9601
Curated Info

16

Zhang X, et al. (2009) Phosphorylation and degradation of MdmX is inhibited by Wip1 phosphatase in the DNA damage response. Cancer Res 69, 7960-8
19808970   Curated Info

17

Ohtsubo C, et al. (2009) Cytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2. Cancer Sci 100, 1291-9
19432880   Curated Info

18

Zuckerman V, et al. (2009) c-Abl phosphorylates Hdmx and regulates its interaction with p53. J Biol Chem 284, 4031-9
19075013   Curated Info

19

Lopez-Pajares V, Kim MM, Yuan ZM (2008) Phosphorylation of MDMX mediated by Akt leads to stabilization and induces 14-3-3 binding. J Biol Chem 283, 13707-13
18356162   Curated Info

20

Pereg Y, et al. (2006) Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage. Mol Cell Biol 26, 6819-31
16943424   Curated Info

21

Jin Y, et al. (2006) 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J 25, 1207-18
16511572   Curated Info

22

LeBron C, Chen L, Gilkes DM, Chen J (2006) Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. EMBO J 25, 1196-206
16511560   Curated Info

23

Okamoto K, et al. (2005) DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation. Mol Cell Biol 25, 9608-20
16227609   Curated Info

24

Chen L, et al. (2005) ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. EMBO J 24, 3411-22
16163388   Curated Info

25

Pereg Y, et al. (2005) Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage. Proc Natl Acad Sci U S A 102, 5056-61
15788536   Curated Info