Alternative titles; symbols
HGNC Approved Gene Symbol: YBX1
Cytogenetic location: 1p34.2 Genomic coordinates (GRCh38): 1:42,682,418-42,703,805 (from NCBI)
The expression of HLA class II genes is regulated by a series of cis-acting elements and transacting factors. Several cis-acting elements have been identified and have been termed the Z box, X box, Y box, octamer, and TATA box. The Y box contains an inverted CCAAT box. Didier et al. (1988) isolated a cDNA encoding a Y box-binding protein designated YB1, or NSEP1. YB1 binding has an absolute requirement for the CCAAT box and relative specificity for the Y box. It has a molecular mass of 35,414 and contains 18% basic residues and putative nuclear localization signals. Didier et al. (1988) found an inverse correlation of YB1 and HLA-DR(beta) mRNA levels, suggesting that YB1 is a negative regulatory factor.
By screening a human placenta cDNA expression library with DNA fragments containing either the human epidermal growth factor receptor (EGFR; 131550) enhancer or the human c-erbB2 (164870) promoter, Sakura et al. (1988) isolated cDNAs encoding DBPA (603437) and DBPB (NSEP1). The deduced DBPA and DBPB proteins share a central region in which 100 of 109 amino acids are identical between the 2 proteins. Northern blot analysis of HeLa cell RNA detected a 2.3-kb DBPB transcript.
Spitkovsky et al. (1992) cloned cDNAs encoding YB1 by screening a HeLa cell cDNA expression library with an oligonucleotide containing a YB1 recognition site from the human papillomavirus type 18 enhancer. They stated that the sequences of their cDNAs are identical to the sequence of DBPB (Sakura et al., 1988) and nearly identical to the sequence of the YB1 cDNA isolated by Didier et al. (1988). Northern blot analysis of RNAs from a 24-week-old human fetus showed differential expression of the YB1 gene. Immunoblot analysis of HeLa cell and fibroblast extracts using antibodies against a YB1 synthetic peptide identified a 42-kD nuclear protein.
Using an oligonucleotide containing the NSE of the MYC gene (190080) gene as probe, Kolluri and Kinniburgh (1991) cloned NSEP1 from a HeLa cell cDNA expression library. The deduced 322-amino acid protein contains 4 putative DNA-binding domains, 3 of which are rich in basic amino acids. Two of these basic regions, basic-1 and basic-2, form the double-strand DNA-binding domain of the protein. NSEP1 also has a pro/ser/thr-rich domain and an asp/glu/gln-rich domain, both of which are reminiscent of activation domains. It also contains an octapeptide single-strand DNA-binding motif that shares weak homology with the ribonucleoprotein consensus sequence of RNA-binding proteins.
Kudo et al. (1995) isolated human cDNAs encoding DBPA and DBPB by screening for proteins that bind to the human leukosialin (182160) promoter. Northern blot analysis of human tissues detected the highest DBPB expression levels in skeletal muscle and heart. The authors isolated several DBPB processed pseudogenes and determined that they map to many different chromosomes.
Coles et al. (1996) isolated human DBPA and DBPB cDNAs by screening for proteins that are able to bind to the repressor element in the human GMCSF (138960) promoter. The deduced 324-amino acid DBPB protein contains a central cold-shock domain (CSD), which is a highly conserved, approximately 100-amino acid domain with similarity to bacterial cold-shock proteins. Overexpression of DBPB led to repression of the GMCSF promoter.
Fukada and Tonks (2003) found that overexpression of Yb1 in Rat1 cells resulted in increased Ptp1b (176885) expression. Depletion of Yb1 decreased Ptp1b expression, increased sensitivity to insulin, and enhanced signaling through the cytokine receptor gp130 (IL6ST; 600694), which was suppressed by reexpression of Ptp1b. Fukada and Tonks (2003) also found a correlation between expression of PTP1B and YB1 in several human cancer cell lines and in an animal model of type II diabetes (see 125853). They concluded that YB1 is an important regulator of PTP1B expression.
Bhullar and Sollars (2011) found that Ybx1 was highly expressed in mouse erythroid myeloid lymphoid clone-1 (EML), a hematopoietic precursor cell line, but that it was downregulated in myeloid progenitors and in Gmcsf-treated EML cells during myeloid differentiation. Lineage-negative/Il7R (146661)-negative/Kit (164920)-positive/Sca1-positive cells and lineage-negative/Il7r-negative/Kit-positive/Sca1-negative cells expressed high Ybx1 levels compared with differentiated cells, such as granulocytes, in mouse bone marrow. Ybx1 was expressed at high levels in myeloid leukemic cells at different developmental stages. Knockdown of YBX1 in a human leukemic cell line inhibited proliferation ability, induced apoptosis, and induced megakaryocytic differentiation in response to arsenic trioxide treatment. Bhullar and Sollars (2011) concluded that YBX1 is downregulated during myeloid differentiation and that aberrant YBX1 expression in leukemic cells may contribute to leukemia development by blocking differentiation.
Makino et al. (1996) determined the nucleotide sequence of the first exon and of 2,000 upstream nucleotides of the YB1 gene. The first exon is unusually large and contains 166-bp coding sequence and a 331-bp untranslated region. The GC content around the first exon is approximately 70% and a CpG-free region was located in the untranslated sequence. The segment preceding the major transcription initiation site does not contain a TATA box, CCAAT box, or binding sequence for known transcription factors. A transient expression assay using the chloramphenicol acetyltransferase (CAT) gene showed that the sequence from +24 to +281 was critical for CAT expression. PCR analysis on other genomic phage DNAs showed that several clones were derived from pseudogenes.
Kudo et al. (1995) mapped the human NSEP1 gene to 1p34-p33 using in situ hybridization. By fluorescence in situ hybridization, Makino et al. (1996) mapped the NSEP1 gene to 1p34.
Bhullar, J., Sollars, V. E. YBX1 expression and function in early hematopoiesis and leukemic cells. Immunogenetics 63: 337-350, 2011. [PubMed: 21369783] [Full Text: https://doi.org/10.1007/s00251-011-0517-9]
Coles, L. S., Diamond, P., Occhiodoro, F., Vadas, M. A., Shannon, M. F. Cold shock domain proteins repress transcription from the GM-CSF promoter. Nucleic Acids Res. 24: 2311-2317, 1996. [PubMed: 8710501] [Full Text: https://doi.org/10.1093/nar/24.12.2311]
Didier, D. K., Schiffenbauer, J., Woulfe, S. L., Zacheis, M., Schwartz, B. D. Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box. Proc. Nat. Acad. Sci. 85: 7322-7326, 1988. [PubMed: 3174636] [Full Text: https://doi.org/10.1073/pnas.85.19.7322]
Fukada, T., Tonks, N. K. Identification of YB-1 as a regulator of PTP1B expression: implications for regulation of insulin and cytokine signaling. EMBO J. 22: 479-493, 2003. [PubMed: 12554649] [Full Text: https://doi.org/10.1093/emboj/cdg067]
Kolluri, R., Kinniburgh, A. J. Full length cDNA sequence encoding a nuclease-sensitive element DNA binding protein. Nucleic Acids Res. 19: 4771 only, 1991. [PubMed: 1891370] [Full Text: https://doi.org/10.1093/nar/19.17.4771]
Kudo, S., Mattei, M.-G., Fukuda, M. Characterization of the gene for dbpA, a family member of the nucleic-acid-binding proteins containing a cold-shock domain. Europ. J. Biochem. 231: 72-82, 1995. [PubMed: 7628487] [Full Text: https://doi.org/10.1111/j.1432-1033.1995.tb20672.x]
Makino, Y., Ohga, T., Toh, S., Koike, K., Okumura, K., Wada, M., Kuwano, M., Kohno, K. Structural and functional analysis of the human Y-box binding protein (YB-1) gene promoter. Nucleic Acids Res. 24: 1873-1878, 1996. [PubMed: 8657568] [Full Text: https://doi.org/10.1093/nar/24.10.1873]
Sakura, H., Maekawa, T., Imamoto, F., Yasuda, K., Ishii, S. Two human genes isolated by a novel method encode DNA-binding proteins containing a common region of homology. Gene 73: 499-507, 1988. [PubMed: 2977358] [Full Text: https://doi.org/10.1016/0378-1119(88)90514-8]
Spitkovsky, D. D., Royer-Pokora, B., Delius, H., Kisseljov, F., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Royer, H.-D. Tissue restricted expression and chromosomal localization of the YB-1 gene encoding a 42kD nuclear CCAAT binding protein. Nucleic Acids Res. 20: 797-803, 1992. [PubMed: 1542575] [Full Text: https://doi.org/10.1093/nar/20.4.797]