EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1

Fu, Xinyu; McGrath, Shannon; Pasillas, Martina P.; Nakazawa, Shinpei; Kamps, Mark P.

doi:10.1038/sj.onc.1202874

Cited by 31 publications

(26 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of genes speci®cally expressed in t(1;19) cell lines were identi®ed, and two in particular have been characterized in detail; EB-1 (Fu et al, 1999a) and Wnt16 (McWhirter et al, 1999). EB-1 encodes a phosphotyrosine binding domain protein, and as such may have a role in the regulation of cell proliferation.…”

Section: Downstream Target Genesmentioning

confidence: 99%

The role of E2A-PBX1 in leukemogenesis

2001

View full text Add to dashboard Cite

Section: Downstream Target Genesmentioning

confidence: 99%

The role of E2A-PBX1 in leukemogenesis

2001

View full text Add to dashboard Cite

“…Fu and Kamps (1997) first analysed genes induced by E2a-Pbx1 in fibroblasts and identified some tissue-specific and developmentally regulated genes. In human t(1;19)-containing pre-B-cell ALL, they reported that EB-1 overexpression could interfere with proliferation (Fu et al, 1999). Recently, Smith et al (2003) demonstrated that E2a-Pbx1 induction enhances expression of Bmi-1, a lymphoid oncogene whose product functions as a transcriptional Wnt16a-specific siRNA and 16b: Wnt16b-specific siRNA) and, 3 days afterwards, RNA was extracted, quantified and an RT-PCR was performed using the same primers as previously described.…”

mentioning

confidence: 99%

Inhibition of Wnt16 in human acute lymphoblastoid leukemia cells containing the t(1;19) translocation induces apoptosis

Mazières

et al. 2005

Oncogene

View full text Add to dashboard Cite

The Wnt family of secreted glycoproteins is widely involved in cell proliferation, differentiation and oncogenesis. Many Wnt signaling genes are upregulated and activated in chronic lymphocytic leukemia. Less is known concerning acute leukemia. One subtype of acute lymphoblastoid leukemia (ALL) is characterized by a t(1;19) chromosomal translocation resulting in a fusion protein E2A-Pbx1 that promotes transformation and leukemogenesis. Wnt16 has been shown to be targeted by E2A-Pbx1. We performed a differential gene expression array in acute leukemia cell lines displaying or not displaying the t(1;19) translocation. We found that Wnt16 and many Wnt signaling-related genes were upregulated in the translocation-containing cells. As two isoforms of Wnt16, Wnt16a and Wnt16b, have been recently identified, we demonstrated by using RT-PCR and Western blot that Wnt16b (and not Wnt16a) is overexpressed in t(1;19)-containing cell lines. We then directly addressed the role played by both isoforms in this type of leukemia. Using specific short interfering RNA (siRNA) and an antiWnt16 antibody, we showed that targeted-Wnt16b inhibition leads to apoptotic cell death. We also demonstrated that Wnt16b mediates its effect through the canonical Wnt pathway involving dishevelled-2, b-catenin and survivin. We thus propose that Wnt16 plays an important role in leukemogenesis, raising its therapeutic interest.

show abstract

“…The Glut 1 C-terminal-binding protein (GLUT1CBP), also known as SEMCAP-1, and the Jun Nterminal kinase-interacting proteins (JIP)-1 and -2 have been uncovered as adaptors of megalin in previous screens (Gotthardt et al, 2001). E2a-Pbx 1-activated protein (EB-1), a PTB domain protein that is upregulated in pre-B-cell acute lymphocytic leukemia (Fu et al, 1999) has not been identified as interaction partner before. In addition, a partial cDNA sequence, tentatively titled megalin-binding protein (MegBP), was isolated (Table 1; Fig.…”

Section: Resultsmentioning

confidence: 99%

Functional interaction of megalin with the megalinbinding protein(MegBP), a novel tetratrico peptide repeat-containing adaptor molecule

Petersen

Hilpert

Militz

et al. 2003

Journal of Cell Science

View full text Add to dashboard Cite

Megalin is a member of the LDL receptor gene family that plays an important role in forebrain development and in cellular vitamin D metabolism through endocytic uptake of vitamin D metabolites. Similar to other receptors in this gene family, megalin is believed to functionally interact with intracellular proteins through adaptors that bind to the receptor tail and regulate its endocytic and signal transducing activities. Using yeast two-hybrid screens,we identified a novel scaffold protein with tetratrico peptide repeats, the megalin-binding protein (MegBP) that associates with the receptor. The binding site of MegBP was mapped to an N-terminal region on the receptor tail harboring a proline-rich peptide element. MegBP binding did not block the endocytic activity of the receptor; however, overexpression resulted in cellular lethality. In further screens, we identified proteins that bound to MegBP and thus might be recruited to the megalin tail. MegBP-interacting partners included several transcriptional regulators such as the SKI-interacting protein (SKIP), a co-activator of the vitamin D receptor. These finding suggest a model whereby megalin directly participates in transcriptional regulation through controlled sequestration or release of transcription factors via MegBP.

show abstract

EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1

Cited by 31 publications

References 48 publications

The role of E2A-PBX1 in leukemogenesis

The role of E2A-PBX1 in leukemogenesis

Inhibition of Wnt16 in human acute lymphoblastoid leukemia cells containing the t(1;19) translocation induces apoptosis

Functional interaction of megalin with the megalinbinding protein(MegBP), a novel tetratrico peptide repeat-containing adaptor molecule

Contact Info

Product

Resources

About