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Molecule Details

General Information of the Molecule
Name
Cyclin-dependent kinase 6 (CDK6)
Synonyms
Serine/threonine-protein kinase PLSTIRE; Serine/threonine protein kinase PLSTIRE; Cell division protein kinase 6; CDKN6
Gene Name
CDK6
Gene ID
1021
Sequence
MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIR
EVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTE
TIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVV
VTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDVIGLPGE
EDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPYF
QDLERCKENLDSHLPPSQNTSELNTA
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Function
Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e. g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases. Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.
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Uniprot ID
CDK6_HUMAN
EC Number
EC: 2.7.11.22
Pfam
PF00069
KEGG ID
hsa1021
TTD ID
T89361
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gamma tocotrienol   NP Info  + GW9662   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gingerol   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Erlotinib   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Methylglyoxal   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Elemene   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Piperine   NP Info  + Temozolomide   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Betulinic Acid   NP Info  + Gefitinib   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Pterostilbene   NP Info  + Sorafenib   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Capsaicin   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Expression of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Capsaicin   NP Info  + 3,3'-diindolylmethane   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Expression of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Chrysin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Apigenin   NP Info  + Cisplatin   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Apigenin  NP Info  Investigative Psilotum nudum
2 Chrysin  NP Info  Investigative Tripterygium wilfordii
3 Fisetin  NP Info  Investigative Toxicodendron succedaneum
References
Reference 1 Synergistic Antiproliferative Effects of Combined Gamma -Tocotrienol and PPAR Gamma Antagonist Treatment Are Mediated through PPAR Gamma -Independent Mechanisms in Breast Cancer Cells. PPAR Res. 2014;2014:439146.
Reference 2 Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells. Oncol Lett. 2016 May;11(5):3527-3533.
Reference 3 [10]-Gingerol improves doxorubicin anticancer activity and decreases its side effects in triple negative breast cancer models. Cell Oncol (Dordr). 2020 Oct;43(5):915-929.
Reference 4 Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells. Environ Toxicol. 2018 Nov;33(11):1153-1159.
Reference 5 Methylglyoxal in combination with 5-Fluorouracil elicits improved chemosensitivity in breast cancer through apoptosis and cell cycle inhibition. Biomed Pharmacother. 2019 Jun;114:108855.
Reference 6 beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis. Oncol Rep. 2009 Jul;22(1):161-70.
Reference 7 Piperine synergistically enhances the effect of temozolomide against temozolomide-resistant human glioma cell lines. Bioengineered. 2020 Dec;11(1):791-800.
Reference 8 Pterostilbene enhances sorafenib's anticancer effects on gastric adenocarcinoma. J Cell Mol Med. 2020 Nov;24(21):12525-12536.
Reference 9 Capsaicin induces apoptosis of cisplatin-resistant stomach cancer cells by causing degradation of cisplatin-inducible Aurora-A protein. Nutr Cancer. 2011;63(7):1095-103.
Reference 10 Synergistic anticancer activity of capsaicin and 3,3'-diindolylmethane in human colorectal cancer. J Agric Food Chem. 2015 May 6;63(17):4297-304.
Reference 11 Potentiating activities of chrysin in the therapeutic efficacy of 5-fluorouracil in gastric cancer cells. Oncol Lett. 2021 Jan;21(1):24.
Reference 12 Protective effects of apigenin and myricetin against cisplatin-induced nephrotoxicity in mice. Pharm Biol. 2017 Dec;55(1):766-774.
Reference 13 Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. J Med Chem. 2005 Feb 10;48(3):737-43.
Reference 14 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China