Thr286
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Home > Phosphorylation Site Page: > Thr286  -  CCND1 (human)

Site Information
EEVDLACtPtDVRDV   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447839

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 13 , 19 ) , flow cytometry ( 5 ) , immunoprecipitation ( 5 ) , mass spectrometry ( 1 , 2 , 3 , 7 , 9 ) , microscopy-colocalization with upstream kinase ( 15 ) , mutation of modification site ( 5 , 7 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 , 21 , 22 ) , phospho-antibody ( 6 , 8 , 11 , 12 , 16 , 20 , 21 ) , western blotting ( 5 , 6 , 8 , 11 , 12 , 15 , 16 , 22 )
Disease tissue studied:
bone cancer ( 5 , 22 ) , breast cancer ( 2 , 6 , 17 ) , breast ductal carcinoma ( 2 ) , HER2 positive breast cancer ( 1 ) , luminal A breast cancer ( 1 ) , luminal B breast cancer ( 1 ) , breast cancer, triple negative ( 1 ) , pancreatic cancer ( 9 ) , prostate cancer ( 12 ) , cancer, squamous cell carcinoma ( 7 ) , thyroid cancer ( 16 ) , Down syndrome ( 5 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
GSK3B (human) ( 13 )
Putative in vivo kinases:
DYRK1A (human) ( 5 ) , GSK3B (human) ( 13 ) , IKKA (human) ( 19 )
Kinases, in vitro:
DYRK1A (human) ( 5 ) , GSK3B (human) ( 15 , 22 ) , IKKA (human) ( 19 )
Treatments:
bassiatin ( 6 ) , BIM-23120 ( 16 ) , cycloheximide ( 15 ) , DIF-3 ( 13 ) , IL-1b ( 8 ) , lithium ( 13 ) , mechanical stress ( 8 ) , somatostatin ( 16 ) , STG28 ( 12 )

Downstream Regulation
Effects of modification on CCND1:
intracellular localization ( 12 , 13 , 15 , 17 , 21 ) , molecular association, regulation ( 7 , 12 , 14 , 21 ) , protein degradation ( 5 , 11 , 12 , 13 , 14 , 18 , 20 , 22 ) , ubiquitination ( 11 )
Effects of modification on biological processes:
cell cycle regulation ( 5 , 15 ) , cell growth, altered ( 15 )
Induce interaction with:
BTRC (human) ( 12 ) , CRYAB (mouse) ( 14 ) , Exportin-1 (human) ( 21 ) , FBXO31 (human) ( 11 )
Inhibit interaction with:
CDK4 (mouse) ( 7 ) , PRMT5 (mouse) ( 7 ) , SMARCA4 (mouse) ( 7 ) , WDR77 (mouse) ( 7 )

References 

1

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

2

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

3

Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62
24275569   Curated Info

4

Ullal AV, et al. (2014) Cancer cell profiling by barcoding allows multiplexed protein analysis in fine-needle aspirates. Sci Transl Med 6, 219ra9
24431113   Curated Info

5

Chen JY, Lin JR, Tsai FC, Meyer T (2013) Dosage of Dyrk1a shifts cells within a p21-cyclin D1 signaling map to control the decision to enter the cell cycle. Mol Cell 52, 87-100
24119401   Curated Info

6

Meng L, et al. (2011) A novel antioestrogen agent (3R,6R)-bassiatin inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression in 17β-oestradiol-treated MCF-7 cells. Cell Biol Int 35, 599-605
21241249   Curated Info

7

Aggarwal P, et al. (2010) Nuclear cyclin D1/CDK4 kinase regulates CUL4 expression and triggers neoplastic growth via activation of the PRMT5 methyltransferase. Cancer Cell 18, 329-40
20951943   Curated Info

8

Liu J, Agarwal S (2010) Mechanical signals activate vascular endothelial growth factor receptor-2 to upregulate endothelial cell proliferation during inflammation. J Immunol 185, 1215-21
20548028   Curated Info

9

Tucker M (2010) CST Curation Set: 9828; Year: 2010; Biosample/Treatment: tissue, pancreas/untreated; Disease: pancreatic cancer; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]P
Curated Info

10

Barbash O, et al. (2009) Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation. Oncogene 28, 4317-25
19767775   Curated Info

11

Santra MK, Wajapeyee N, Green MR (2009) F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature 459, 722-5
19412162   Curated Info

12

Wei S, et al. (2008) A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells. J Biol Chem 283, 26759-70
18650423   Curated Info

13

Takahashi-Yanaga F, et al. (2006) Involvement of GSK-3beta and DYRK1B in differentiation-inducing factor-3-induced phosphorylation of cyclin D1 in HeLa cells. J Biol Chem 281, 38489-97
17046823   Curated Info

14

Lin DI, et al. (2006) Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell 24, 355-66
17081987   Curated Info

15

Benzeno S, et al. (2006) Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1. Oncogene 25, 6291-303
16732330   Curated Info

16

Tagliati F, et al. (2006) Role of complex cyclin d1/cdk4 in somatostatin subtype 2 receptor-mediated inhibition of cell proliferation of a medullary thyroid carcinoma cell line in vitro. Endocrinology 147, 3530-8
16601140   Curated Info

17

Alao JP, et al. (2006) Histone deacetylase inhibitor, trichostatin A induces ubiquitin-dependent cyclin D1 degradation in MCF-7 breast cancer cells. Mol Cancer 5, 8
16504004   Curated Info

18

Mori J, et al. (2005) Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr286 in squamous cell carcinoma. Exp Cell Res 310, 426-33
16153639   Curated Info

19

Kwak YT, et al. (2005) IkappaB kinase alpha regulates subcellular distribution and turnover of cyclin D1 by phosphorylation. J Biol Chem 280, 33945-52
16103118   Curated Info

20

Guo Y, et al. (2005) Phosphorylation of cyclin D1 at Thr 286 during S phase leads to its proteasomal degradation and allows efficient DNA synthesis. Oncogene 24, 2599-612
15735756   Curated Info

21

Alt JR, Gladden AB, Diehl JA (2002) p21(Cip1) Promotes cyclin D1 nuclear accumulation via direct inhibition of nuclear export. J Biol Chem 277, 8517-23
11751903   Curated Info

22

Germain D, Russell A, Thompson A, Hendley J (2000) Ubiquitination of free cyclin D1 is independent of phosphorylation on threonine 286. J Biol Chem 275, 12074-9
10766840   Curated Info