Molecule Information

General Information of the Molecule (ID: Mol00198)

• Name: Protein zeta/delta 14-3-3 (YWHAZ) ,Homo sapiens
• Synonyms: Protein kinase C inhibitor protein 1; KCIP-1
• Molecule Type: Protein
• Gene Name: YWHAZ
• Gene ID: 7534
• Location: chr8:100916523-100953388[-]
• Sequence:
  MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWR
  VVSSIEQKTEGAEKKQQMAREYREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLK
  MKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFYYE
  ILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAG
  EGGEN
• Function: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation. In neurons, regulates spine maturation through the modulation of ARHGEF7 activity.
• Uniprot ID: 1433Z_HUMAN
• Ensembl ID: ENSG00000164924
• HGNC ID: HGNC:12855

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: p38/MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Down-regulation of miR-30c correlated with overexpression of YWHAZ in breast doxorubicin-resistant cells, Overexpression of miR-30c sensitized MCF-7/ADR cells to doxorubicin, miR-30c suppressed expression of the YWHAZ gene, YWHAZ was a key signal molecule in doxorubicin resistance by reducing activation of the p38MAPk signal pathway in MCF-7/ADR cells, miR-30c regulated doxorubicin resistance in vivo.

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: T-cell lymphoma [2]

• Resistant Disease: T-cell lymphoma [ICD-11: 2A60.3]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: YTS cells; Pleural effusion; Homo sapiens (Human); CVCL_D324
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Compared with YTS-gem cells, the level of Pro apoptotic protein Bax in YTS gem cells that down regulated 14-3-3-Zetawas significantly higher. In contrast, the levels of anti apoptotic proteins Bcl-2, Caspase-3, cleaved caspase-3 and cyclin D1 decreased significantly.

Disease Class: Extranodal NK/T-cell lymphoma [2]

• Resistant Disease: Extranodal NK/T-cell lymphoma [ICD-11: 2A90.6]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: YTS cells; Pleural effusion; Homo sapiens (Human); CVCL_D324
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: 14-3-3-Zeta was up regulated in YTS gem cells, 14-3-3-Zeta promote cell proliferation and invasion, 14-3-3-Zeta protein induced enktl resistance to gemcitabine through anti apoptotic pathway.

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [3]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Beta-catenin signaling pathway; Inhibition; hsa04520
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Luciferase reporter assay; RT-PCR; Western blot analysis
• Experiment for Drug Resistance: Muse Cell Cycle Assay
• Mechanism Description: miR451 suppresses cell migration, invasion and induces cell-cycle arrest and apoptosis in breast cancermiR451 decreases the mRNA and protein expression level of beta-catenin and relative genes of beta-catenin signaling pathway in vitro.

Tamoxifen

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [4]

• Sensitive Disease: Breast cancer [ICD-11: 2C60.3]
• Sensitive Drug: Tamoxifen
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Regulation; hsa04150
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: LCC2 cells; Breast; Homo sapiens (Human); CVCL_DP51
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Over-expression of miR-451a can enhance MCF-7 and LCC2 cell sensitivity to TAM. Opposite effects were elicited by knocking down miR-451a. TAM treatment can up-regulate 14-3-3Zeta expression, and down-regulate ERalpha expression. 14-3-3Zeta and ERalpha were shown to interact. Over-expression of miR-451a decreased 14-3-3Zeta expression and increased ERalpha expression, suppressing cell proliferation, increasing apoptosis, and reducing activation of p-AkT and p-mTOR.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.22E-47; Fold-change: 7.81E-01; Z-score: 1.21E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.90E-07; Fold-change: 5.20E-01; Z-score: 7.06E-01

References

• Ref 1: Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells. Braz J Med Biol Res. 2014 Jan;47(1):60-9. doi: 10.1590/1414-431X20133324. Epub 2014 Jan 10.
• Ref 2: [14-3-3Zeta protein mediates gemcitabine resistance in NK/T-cell lymphoma] .Zhonghua Xue Ye Xue Za Zhi. 2019 Nov 14;40(11):906-911. doi: 10.3760/cma.j.issn.0253-2727.2019.11.004. 10.3760/cma.j.issn.0253-2727.2019.11.004
• Ref 3: Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer. Cell Death Dis. 2017 Oct 5;8(10):e3071. doi: 10.1038/cddis.2017.460.
• Ref 4: Over-expression of miR-451a can enhance the sensitivity of breast cancer cells to tamoxifen by regulating 14-3-3 Zeta, estrogen receptor Alpha, and autophagy. Life Sci. 2016 Mar 15;149:104-13. doi: 10.1016/j.lfs.2016.02.059. Epub 2016 Feb 17.