Docetaxel (T3D3501)

General Function:

Zinc ion binding

Specific Function:

Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.

Gene Name:

NR1I2

Uniprot ID:

O75469

Molecular Weight:

49761.245 Da

References

1. Ikezoe T, Hisatake Y, Takeuchi T, Ohtsuki Y, Yang Y, Said JW, Taguchi H, Koeffler HP: HIV-1 protease inhibitor, ritonavir: a potent inhibitor of CYP3A4, enhanced the anticancer effects of docetaxel in androgen-independent prostate cancer cells in vitro and in vivo. Cancer Res. 2004 Oct 15;64(20):7426-31. [15492266 ]
2. Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. [18839173 ]

General Function:

Ubiquitin protein ligase binding

Specific Function:

Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.

Gene Name:

EGFR

Uniprot ID:

P00533

Molecular Weight:

134276.185 Da

References

1. Buchholz S, Schally AV, Engel JB, Hohla F, Heinrich E, Koester F, Varga JL, Halmos G: Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1943-6. Epub 2007 Jan 29. [17261802 ]

General Function:

Peptide hormone binding

Specific Function:

Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion.

Gene Name:

GHRHR

Uniprot ID:

Q02643

Molecular Weight:

47401.53 Da

References

1. Buchholz S, Schally AV, Engel JB, Hohla F, Heinrich E, Koester F, Varga JL, Halmos G: Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1943-6. Epub 2007 Jan 29. [17261802 ]

General Function:

Protein kinase binding

Specific Function:

Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.

Gene Name:

KIF11

Uniprot ID:

P52732

Molecular Weight:

119158.025 Da

References

1. Luo L, Parrish CA, Nevins N, McNulty DE, Chaudhari AM, Carson JD, Sudakin V, Shaw AN, Lehr R, Zhao H, Sweitzer S, Lad L, Wood KW, Sakowicz R, Annan RS, Huang PS, Jackson JR, Dhanak D, Copeland RA, Auger KR: ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism. Nat Chem Biol. 2007 Nov;3(11):722-6. Epub 2007 Oct 7. [17922005 ]

General Function:

Structural molecule activity

Specific Function:

The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules.

Gene Name:

MAP2

Uniprot ID:

P11137

Molecular Weight:

199524.51 Da

References

1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. [18068131 ]

General Function:

Structural molecule activity

Specific Function:

Non-neuronal microtubule-associated protein. Promotes microtubule assembly.

Gene Name:

MAP4

Uniprot ID:

P27816

Molecular Weight:

121003.805 Da

References

1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. [18068131 ]

General Function:

Structural constituent of cytoskeleton

Specific Function:

Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.

Gene Name:

MAPT

Uniprot ID:

P10636

Molecular Weight:

78927.025 Da

References

1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. [18068131 ]

General Function:

Ubiquitin protein ligase binding

Specific Function:

Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).

Gene Name:

BCL2

Uniprot ID:

P10415

Molecular Weight:

26265.66 Da

General Function:

Structural constituent of cytoskeleton

Specific Function:

Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).

Gene Name:

TUBB1

Uniprot ID:

Q9H4B7

Molecular Weight:

50326.56 Da