Tyr33
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Home > Phosphorylation Site Page: > Tyr33  -  WWOX (human)

Site Information
TTkDGWVyYANHTEE   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449043

In vivo Characterization
Methods used to characterize site in vivo:
immunoassay ( 2 ) , immunoprecipitation ( 4 , 7 , 10 ) , mass spectrometry (in vitro) ( 1 ) , microscopy-colocalization with upstream kinase ( 13 , 15 , 16 ) , mutation of modification site ( 3 , 4 , 7 , 9 , 11 , 12 , 17 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 18 ) , western blotting ( 2 , 3 , 4 , 6 , 7 , 8 , 9 , 14 , 16 , 18 )
Disease tissue studied:
Alexander's disease ( 16 ) , Alzheimer's disease ( 7 ) , breast cancer ( 2 , 3 , 14 ) , breast ductal carcinoma ( 14 ) , colorectal cancer ( 2 , 4 , 9 ) , colorectal carcinoma ( 2 , 4 , 9 ) , liver cancer ( 8 ) , hepatocellular carcinoma ( 8 ) , lung cancer ( 3 ) , non-small cell lung cancer ( 3 ) , lymphoma ( 18 ) , neuroblastoma ( 7 , 10 , 14 , 16 , 18 ) , prostate cancer ( 14 , 18 ) , fibrosarcoma of soft tissue ( 3 , 4 , 9 ) , cancer, squamous cell carcinoma ( 2 , 13 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
FAM189B (human) ( 8 ) , WWOX (human) ( 13 )
Putative in vivo kinases:
Src (human) ( 17 )
Kinases, in vitro:
Src (human) ( 17 )
Treatments:
androsterone ( 14 ) , anisomycin ( 18 ) , ceritinib ( 2 ) , estradiol ( 14 ) , light ( 15 ) , MPP+ ( 10 ) , siRNA ( 13 ) , UV ( 11 , 13 , 18 )

Downstream Regulation
Effects of modification on WWOX:
enzymatic activity, induced ( 10 ) , intracellular localization ( 4 , 9 , 10 , 11 , 15 ) , molecular association, regulation ( 1 , 3 , 4 , 9 , 10 , 11 , 17 , 18 ) , protein conformation ( 1 )
Effects of modification on biological processes:
apoptosis, altered ( 9 , 10 ) , apoptosis, induced ( 2 , 3 , 8 , 13 , 15 , 17 , 18 ) , carcinogenesis, inhibited ( 2 , 3 ) , cell growth, induced ( 6 ) , cell growth, inhibited ( 2 ) , cell motility, inhibited ( 3 ) , signaling pathway regulation ( 2 ) , transcription, induced ( 3 )
Induce interaction with:
HYAL2 (human) ( 4 ) , HYAL2 (mouse) ( 9 ) , JNK1 (human) ( 18 ) , TIAF1 (human) ( 3 ) , p53 (human) ( 3 , 11 ) , p73 (human) ( 17 )
Inhibit interaction with:
JNK1 (human) ( 10 ) , p73 (human) ( 1 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 16 ) , prostate cancer ( 14 ) , cancer, squamous cell carcinoma ( 13 ) , Parkinson's disease ( 10 ) , occular surface disease ( 6 )

References 

1

Lahav N, et al. (2020) Phosphorylation of the WWOX protein regulates its interaction with p73. Chembiochem
32185845   Curated Info

2

Wang WJ, et al. (2019) WWOX Possesses -Terminal Cell Surface-Exposed Epitopes WWOX and WWOX for Signaling Cancer Growth Suppression and Prevention In Vivo. Cancers (Basel) 11
31752354   Curated Info

3

Chou PY, et al. (2019) A p53/TIAF1/WWOX triad exerts cancer suppression but may cause brain protein aggregation due to p53/WWOX functional antagonism. Cell Commun Signal 17, 76
31315632   Curated Info

4

Hsu LJ, et al. (2017) Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. Oncotarget 8, 19137-19155
27845895   Curated Info

5

Chang JY, et al. (2015) Trafficking protein particle complex 6A delta (TRAPPC6AΔ) is an extracellular plaque-forming protein in the brain. Oncotarget 6, 3578-89
25650666   Curated Info

6

Huang YH, Chang NS, Tseng SH (2015) Expression of WW domain-containing oxidoreductase WWOX in pterygium. Mol Vis 21, 711-7
26120275   Curated Info

7

Chang JY, Chang NS (2015) WWOX dysfunction induces sequential aggregation of TRAPPC6AΔ, TIAF1, tau and amyloid β, and causes apoptosis. Cell Death Discov 1, 15003
27551439   Curated Info

8

Zhang H, et al. (2014) Upregulation of the putative oncogene COTE1 contributes to human hepatocarcinogenesis through modulation of WWOX signaling. Int J Oncol 45, 719-31
24899407   Curated Info

9

Hsu LJ, et al. (2009) Transforming growth factor beta1 signaling via interaction with cell surface Hyal-2 and recruitment of WWOX/WOX1. J Biol Chem 284, 16049-59
19366691   Curated Info

10

Lo CP, et al. (2008) MPP+-induced neuronal death in rats involves tyrosine 33 phosphorylation of WW domain-containing oxidoreductase WOX1. Eur J Neurosci 27, 1634-46
18371080   Curated Info

11

Chang NS, et al. (2005) WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53. J Biol Chem 280, 43100-8
16219768   Curated Info

12

Mahajan NP, Whang YE, Mohler JL, Earp HS (2005) Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res 65, 10514-23
16288044   Curated Info

13

Lai FJ, et al. (2005) WOX1 is essential for UVB irradiation-induced apoptosis and down-regulated via translational blockade in UVB-induced cutaneous squamous cell carcinoma in vivo. Clin Cancer Res 11, 5769-77
16115915   Curated Info

14

Chang NS, et al. (2005) 17beta-Estradiol upregulates and activates WOX1/WWOXv1 and WOX2/WWOXv2 in vitro: potential role in cancerous progression of breast and prostate to a premetastatic state in vivo. Oncogene 24, 714-23
15580310   Curated Info

15

Chen ST, et al. (2005) Light-induced retinal damage involves tyrosine 33 phosphorylation, mitochondrial and nuclear translocation of WW domain-containing oxidoreductase in vivo. Neuroscience 130, 397-407
15664696   Curated Info

16

Sze CI, et al. (2004) Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease. J Biol Chem 279, 30498-506
15126504   Curated Info

17

Aqeilan RI, et al. (2004) Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Proc Natl Acad Sci U S A 101, 4401-6
15070730   Curated Info

18

Chang NS, Doherty J, Ensign A (2003) JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis. J Biol Chem 278, 9195-202
12514174   Curated Info