Disease relevance of YBX1

• We now report that, in multidrug-resistant MCF-7 breast cancer cells, nuclear localization of YB-1 is associated with MDR-1 gene expression [1].
• Cooperative action of cellular proteins YB-1 and Pur alpha with the tumor antigen of the human JC polyomavirus determines their interaction with the viral lytic control element [2].
• In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm [3].
• Nuclear expression of Y-box-binding protein-1 correlates with P-glycoprotein and topoisomerase II alpha expression, and with poor prognosis in synovial sarcoma [4].
• Our study suggests that YB-1 expression correlates with Topo IIalpha and PCNA expression in lung cancer [5].

Psychiatry related information on YBX1

• In conclusion, YB-1 demonstrated prognostic and predictive significance in breast cancer by identifying high-risk patients in both the presence and absence of postoperative chemotherapy, independent of tumor-biologic factors currently available for clinical decision making [6].

High impact information on YBX1

• Regulated overexpression of YB-1 in drug-sensitive diploid breast epithelial cells induced MDR-1 gene expression and multidrug resistance [1].
• Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation [7].
• We have now identified two major RNA-binding proteins, nucleolin and YB-1, that specifically bind to the JRE [7].
• During thrombin activation, dbpB was found to be cleaved, yielding a 30-kDa NH(2)-terminal fragment that recognized the thrombin-response element sequence, but not the Y-box consensus sequence [8].
• Preincubation of ECs with protein tyrosine phosphatase inhibitors completely blocked dbpB activation by thrombin and blocked induction of endogenous PDGF B-chain mRNA and promoter activation by thrombin [8].

Chemical compound and disease context of YBX1

• CONCLUSIONS: We hypothesize that early in prostate cancer progression, increased expression of YB-1 may increase P-gp activity which may in turn lower androgen levels in the prostate tumor cells [9].
• We found that trichostatin A upregulated CAR expression and that irinotecan caused increased nuclear localization of YB-1 in both glioblastoma cell lines [10].
• We examined the effects of non-cytotoxic and cytotoxic doses of arsenic(III) and chromium(VI) on nuclear binding of the transcription factors AP-1, NF-kappaB, Sp1, and YB-1 in human MDA-MB-435 breast cancer and rat H4IIE hepatoma cells [11].
• Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer [12].

Biological context of YBX1

• These results suggest that YB-1 can function as a recognition protein for cisplatin-damaged DNA and that it may be important in DNA repair or in directing the cellular response to DNA damage [13].
• We previously showed that YB-1 is overexpressed in human cancer cell lines that are resistant to cisplatin and that the depletion of YB-1 by transfection of a vector expressing YB-1 antisense RNA increases the sensitivity of human cancer cells to cisplatin [13].
• The Y-box binding protein (YB-1) binds to inverted CCAAT box sequences that are present in the promoter region of many genes [13].
• Therefore, YB-1 is directly linked to MVP-mediated drug resistance [14].
• In conclusion, YB-1 is a new Akt substrate and disruption of this specific site inhibits tumor cell growth [15].

Anatomical context of YBX1

• We found that breast tumors which were both estrogen receptor-negative and lymph node positive were associated with high YB-1 expression (P=0.017) [16].
• A full-length YB-1 protein expressed in human lung fibroblasts was primarily located in the nucleus with punctate staining in cytoplasmic regions [17].
• Nuclear YB-1 expression had a significant correlation with P-glycoprotein and PgR expression, and also with CD68 grade, concerning accumulation of tumor associated macrophages [18].
• Ectopic expression of YB-1 and Puralpha in glial cells synergistically stimulated viral promoter activity via the 23-bp sequence element [19].
• A yeast interaction trap screen using LexA-YY1 as a bait and a HeLa cell cDNA-acid patch fusion library identified YB-1 as a YY1-interacting protein [20].

Associations of YBX1 with chemical compounds

• In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity [14].
• Tumor-associated p53 mutants however are attenuated for YB1 nuclear localization as are mutants mutated in the proline-rich domain of p53 [21].
• RESULTS: YB-1 expression is markedly increased during benign to malignant transformation and further following androgen ablation [9].
• The Y box-binding protein (YB-1) binds to DNA sequences, present in the control regions of many genes, that contain an inverted CCAAT box [22].
• Electrophoretic mobility shift assays (EMSA) using various IgRE-derived oligonucleotide probes containing serial two-base mutations showed that YB-1 protein was preferentially bound to the pyrimidine-rich sequence within the IgRE [23].

Physical interactions of YBX1

• Ankrd2 binding to the ubiquitous transcription factor YB-1 can be demonstrated both in vitro and in vivo; this is not very surprising, since a similar interaction was previously described for CARP [24].
• Using a yeast one-hybrid screen, we found the transcription factor Y box binding protein 1 (YB-1) interacts with the 5-HTT VNTR [25].
• Transcription factor Y-box-binding protein 1 (YB-1), which binds to the inverted CCAAT box, is not only involved in the transcription of various genes, but also in cell proliferation and DNA repair [26].
• An In vivo coimmunoprecipitation assay showed that IRP2 bound to YB-1 in the presence of iron and a proteasome inhibitor [27].
• We now demonstrate that YB-1 directly interacts with p53 using an in vitro pull-down assay [28].

Regulatory relationships of YBX1

• The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-box transcription factor [1].
• Taken together, our results demonstrate that YB-1 overexpression can induce EGF independence in HMECs via activation of the EGFR pathway [29].
• In the present study, we report that overexpression of a transfected gene encoding YB-1 in human HeLa cervical carcinoma cells significantly represses the transactivation of a minimal AP-1 reporter construct in response to the tumour promoter PMA [30].
• RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells [31].
• Therefore, the increased binding activity seen in TGF-beta-stimulated nuclear extracts was due primarily to relocalization of YB-1 from the cytoplasm to the nuclear compartment [17].

Other interactions of YBX1

• By using JCV as a model, we investigated the role of the viral early protein tumor antigen (TAg) in the binding of two cellular proteins, Pura alpha and YB-1, to JCV regulatory sequences [2].
• Using immunochemical coprecipitation methods, we observed binding of YB-1 and PCNA in vivo [13].
• Interferon-gamma interferes with transforming growth factor-beta signaling through direct interaction of YB-1 with Smad3 [32].
• However, cell growth could be blocked with an ErbB kinase inhibitor, indicating that EGFR signaling plays a major role in YB-1-induced growth factor independence [29].
• Y-box-binding protein 1 confers EGF independence to human mammary epithelial cells [29].

Analytical, diagnostic and therapeutic context of YBX1

• Transient transfection of antisense YB-1 expression constructs resulted in a decrease of both YB-1 protein levels and DNA binding activity to the inverted CCAAT box, as determined by Western blot and gel mobility shift assays [33].
• Interestingly, we found that patients who were on a chemotherapy regime which contained an anthracycline (a Pgp substrate) and subsequently developed recurrence, had a higher YB-1 score compared to patients on the Cyclophosphamide/Methotrexate/5-Fluorouracil regime (P=0.024) [16].
• YB-1 expression in breast cancer may be a potential marker of chemoresistance and could possibly aid in selection of the appropriate adjuvant chemotherapy regime for breast cancers [16].
• Hyperthermia-induced nuclear translocation of transcription factor YB-1 leads to enhanced expression of multidrug resistance-related ABC transporters [34].
• Gel mobility shift assays showed that the interaction of YB-1 with p53 stimulated the sequence-specific DNA binding of p53 to its consensus sequence [28].

References