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Molecule Details

General Information of the Molecule
Name
Ribosomal protein S6 kinase beta-1 (S6K1)
Synonyms
p70-S6K 1; p70 ribosomal S6 kinase alpha; p70 S6KA; p70 S6K-alpha; p70 S6 kinase alpha; Serine/threonine-protein kinase 14A; STK14A; S6K-beta-1; S6K; Ribosomal protein S6 kinase I; P70S6K1; P70-S6K; 70 kDa ribosomal protein S6 kinase 1
Gene Name
RPS6KB1
Gene ID
6198
Sequence
MRRRRRRDGFYPAPDFRDREAEDMAGVFDIDLDQPEDAGSEDELEEGGQLNESMDHGGVG
PYELGMEHCEKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKVTGANTGKIF
AMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSGGEL
FMQLEREGIFMEDTACFYLAEISMALGHLHQKGIIYRDLKPENIMLNHQGHVKLTDFGLC
KESIHDGTVTHTFCGTIEYMAPEILMRSGHNRAVDWWSLGALMYDMLTGAPPFTGENRKK
TIDKILKCKLNLPPYLTQEARDLLKKLLKRNAASRLGAGPGDAGEVQAHPFFRHINWEEL
LARKVEPPFKPLLQSEEDVSQFDSKFTRQTPVDSPDDSTLSESANQVFLGFTYVAPSVLE
SVKEKFSFEPKIRSPRRFIGSPRTPVSPVKFSPGDFWGRGASASTANPQTPVEYPMETSG
IEQMDVTMSGEASAPLPIRQPNSGPYKKQAFPMISKRPEHLRMNL
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Function
Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition.
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Uniprot ID
KS6B1_HUMAN
EC Number
EC: 2.7.11.1
Pfam
PF00069 ; PF00433
KEGG ID
hsa6198
TTD ID
T94479
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 Resveratrol   NP Info  + Doxorubicin   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 Vinblastine   NP Info  + Temsirolimus   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 Cardamonin   NP Info  + Cisplatin   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 Arsenic trioxide   NP Info  + Sorafenib   Drug Info 
                    Structure +
          Phosphorylation Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Phosphorylation of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + Raloxifene   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Phosphorylation of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Phosphorylation of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gossypol   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Phosphorylation of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Cardamonin   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Phosphorylation of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Gefitinib   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Phosphorylation of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Androgen   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Phosphorylation of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Silibinin   NP Info  + Regorafenib   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Phosphorylation of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Emodin   NP Info  + Cytarabine   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Phosphorylation of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Tamoxifen   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Phosphorylation of This Molecule [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Triptolide   NP Info  + BIIB021   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Phosphorylation of This Molecule [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Rapamycin   Drug Info 
                    Structure +
                    Drug Combination 12 Down-regulating the Phosphorylation of This Molecule [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Rapamycin   Drug Info 
                    Structure +
                 Up-regulation     Click to Show/Hide
                    Drug Combination 1 Up-regulating the Phosphorylation of This Molecule [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Capsaicin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 2 Up-regulating the Phosphorylation of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + 2-deoxy-D-glucose   Drug Info 
                    Structure +
                    Drug Combination 3 Up-regulating the Phosphorylation of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Arsenic trioxide   NP Info  + Lonidamine   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Neferine  NP Info  Investigative Nelumbo nucifera
2 Tangeretin  NP Info  Investigative Citrus reticulata
Drug(s) of This Target
1 PD184352  Drug Info  Investigative Chronic lymphocytic leukaemia
References
Reference 1 Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro. Cell Prolif. 2011 Dec;44(6):591-601.
Reference 2 Sustained antitumor activity by co-targeting mTOR and the microtubule with temsirolimus/vinblastine combination in hepatocellular carcinoma. Biochem Pharmacol. 2012 May 1;83(9):1146-58.
Reference 3 Cardamonin enhances the anti-proliferative effect of cisplatin on ovarian cancer. Oncol Lett. 2018 Mar;15(3):3991-3997.
Reference 4 [Inhibitory effect of sorafenib combined with arsenic trioxide on hepatocellular carcinoma cells]. Nan Fang Yi Ke Da Xue Xue Bao. 2008 Apr;28(4):639-41.
Reference 5 The combination of raloxifene and epigallocatechin gallate suppresses growth and induces apoptosis in MDA-MB-231 cells. Life Sci. 2008 Apr 23;82(17-18):943-8.
Reference 6 Synergistic action of genistein and cisplatin on growth inhibition and cytotoxicity of human medulloblastoma cells. Pediatr Neurosurg. 2000 Sep;33(3):123-31.
Reference 7 Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015 Sep;76(3):575-86.
Reference 8 Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death. J Exp Clin Cancer Res. 2019 Jun 13;38(1):254.
Reference 9 Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells. PLoS One. 2012;7(2):e31579.
Reference 10 Regorafenib in combination with silybin as a novel potential strategy for the treatment of metastatic colorectal cancer. Oncotarget. 2017 Aug 7;8(40):68305-68316.
Reference 11 Emodin and Its Combination with Cytarabine Induce Apoptosis in Resistant Acute Myeloid Leukemia Cells in Vitro and in Vivo. Cell Physiol Biochem. 2018;48(5):2061-2073.
Reference 12 Curcumin induces cell death and restores tamoxifen sensitivity in the antiestrogen-resistant breast cancer cell lines MCF-7/LCC2 and MCF-7/LCC9. Molecules. 2013 Jan 8;18(1):701-20.
Reference 13 Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-KappaB signal pathways in thyroid carcinoma cells. Biomed Pharmacother. 2016 Oct;83:22-32.
Reference 14 Arsenic trioxide overcomes rapamycin-induced feedback activation of AKT and ERK signaling to enhance the anti-tumor effects in breast cancer. PLoS One. 2013 Dec 31;8(12):e85995.
Reference 15 Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011 Feb 28;301(2):168-76.
Reference 16 Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy. PLoS One. 2015 May 1;10(5):e0121538.
Reference 17 2-Deoxy-D-glucose cooperates with arsenic trioxide to induce apoptosis in leukemia cells: involvement of IGF-1R-regulated Akt/mTOR, MEK/ERK and LKB-1/AMPK signaling pathways. Biochem Pharmacol. 2012 Dec 15;84(12):1604-16.
Reference 18 Increased apoptotic efficacy of lonidamine plus arsenic trioxide combination in human leukemia cells. Reactive oxygen species generation and defensive protein kinase (MEK/ERK, Akt/mTOR) modulation. Biochem Pharmacol. 2011 Dec 1;82(11):1619-29.
Reference 19 Anti-angiogenesis effect of Neferine via regulating autophagy and polarization of tumor-associated macrophages in high-grade serous ovarian carcinoma. Cancer Lett. 2018 Sep 28;432:144-155.
Reference 20 Tangeretin and its metabolite 4'-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K. Br J Pharmacol. 2011 Apr;162(8):1781-91.
Reference 21 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
Cite NPCDR
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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