A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B all

Kamps, Mark P.; Murre, Cornelis; Sun, Xiao Hong; Baltimore, David

doi:10.1016/0092-8674(90)90658-2

Cited by 675 publications

(442 citation statements)

References 36 publications

Supporting

Mentioning

437

Contrasting

Order By: Relevance

“…However, it remains to be addressed if any of these regions play a role in Fli-1 gene regulation. Since E2A-PBX1 fusion protein is activated in the pre-B cell acute lymphocytic leukemic cell lines 697 and RCH-ACV carrying the t(1;19) chromosome translocation (Kamps et al, 1990;Nourse et al, 1990), we analysed for target sequences of E2A-PBX1 in Fli-1b promoter. Our analysis revealed the presence of two such consensus target sequences, raising the possibility that Fli-1b may be activated by E2A-PBX1 in these pre-B cells.…”

Section: Discussionmentioning

confidence: 99%

Fli-1b is generated by usage of differential splicing and alternative promoter

et al. 1998

View full text Add to dashboard Cite

The proto-oncogene Fli-1, a member of Ets family is rearranged or activated through proviral integration in erythroleukemias, induced by Friends' Murine Leukemia Virus. The DNA binding domain (ETS domain) of Fli-1 is fused to the RNA binding domain of EWS by t(11q24:22q12) chromosomal translocation in Ewing's sarcoma and primitive neuroectodermal tumors. Screening of human cDNA libraries has identi®ed two di erent 5'-termini and alternatively spliced forms of the human Fli-1 gene (Fli-1b), suggesting the possible existence of two independent promoters. The genomic sequence adjacent to the alternate exon of human Fli-1b gene shows functional promoter activity when cloned in promoter-less CAT expression vector and transfected into QT-6 cells. The transcription initiation (CAP) site and minimum promoter region necessary for function were localized. The 5'-¯anking regions of human Fli-1b and mouse Fli-1 show 80% homology suggesting conserved promoter regulatory elements. The Fli-1b 5'-anking sequence lacks canonical TATA or CCAAT boxes but contains a partially conserved TATA-like sequence at position 242. Several transcription factor binding sequences like ATF/CREB, E2A-PBX1, EBP, PEA-3, ETS-2, Sp-1, c-Myc, TBP, GATA-1 and Oct-3 were conserved in the promoter sequence. Functional promoter assays revealed that Fli-1b promoter shows very strong transcriptional activation compared to Fli-1 promoter. We also showed that variant Fli-1b has transcriptional activation properties similar to those of Fli-1. Fli-1b and Fli-1 show di erential expression in various hematopoietic cell lines. This di erential expression and promoter activities of Fli-1 and Fli-1b suggests that several mechanisms are involved in Fli-1 gene regulation which are mediated by many transcription factors.

show abstract

Section: Discussionmentioning

confidence: 99%

Fli-1b is generated by usage of differential splicing and alternative promoter

et al. 1998

View full text Add to dashboard Cite

show abstract

“…They gain both binding avidity and specificity by forming heterodimeric DNA binding complexes with PBX proteins (Chan et al, 1994;Chang et al, 1995;Phelan et al, 1995;Lu and Kamps, 1996). The PBX1 gene was first identified as an oncogenic fusion between the PBX homeodomain and the activation domain of the E2A gene product (Kamps et al, 1990;Nourse et al, 1990). Currently however, the regulatory regions of the few downstream targets for HOX proteins, including targets such as p21 (Bromleigh and Freedman, 2000), p53 (Raman et al, 2000a), the progesterone receptor (Raman et al, 2000b), or FGF (Care et al, 1996), do not appear to contain PBX-HOX binding sites.…”

Section: Introductionmentioning

confidence: 99%

HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

Kömüves

Michael

Arbeit

et al. 2002

Developmental Dynamics

View full text Add to dashboard Cite

The HOX homeodomain proteins are fundamental regulators of organ and tissue development, where they are thought to function as transcription factors, and HOX gene expression has been associated with numerous types of cancers. Previous studies have demonstrated that enforced expression of the HOXB4 protein transforms cultured fibroblasts and leads to a selective expansion of the hematopoietic stem cell pool, suggesting that this protein might play a role in cellular proliferation. In support of this concept, we now show that enforced expression of HOXB4 in human neonatal keratinocytes results in increased cellular proliferation and colony formation as well as decreased expression of the alpha-2-integrin and CD44 cell surface adhesion molecules. We previously have reported HOXB4 gene expression in the basal and suprabasal layers of developing human skin and now show extensive HOXB4 mRNA in psoriatic skin and basal cell carcinoma. In fetal human skin HOXB4 protein expression was both nuclear and cytoplasmic within epidermal basal cells and in hair follicle inner and outer root sheath cells, whereas strong nuclear signals were observed in the bulge region. In adult skin, HOXB4 protein expression was both nuclear and cytoplasmic, but was predominantly localized to the intermediate and differentiated cell layers. In contrast to the striking gradient patterns of HOX gene and protein expression previously described in developing spinal cord and limb, HOXB4 protein was uniformly detected in all regions of the fetal and adult skin. Although little HOXB4 signal localized to proliferative cell layers, as marked by proliferating cell nuclear antigen (PCNA) staining, in normal adult epidermis, nuclear HOXB4 protein expression substantially overlapped with PCNA-positive cell in a series of samples of hyperproliferative skin. Taken together, these data suggest that nuclear HOXB4 protein may play a role in the regulation of cellular proliferation/adhesion in developing fetal human epidermis and in hyperproliferation conditions, including cancers, in adult epidermis.Published 2002 Wiley-Liss, Inc. †

show abstract

“…Pbx1 is a homeodomain (HD) protein ®rst identi®ed as the chromosome one participant of the t(1;19) translocation, which is found in 20% of pediatric pre-B cell acute lymphocytic leukemia (ALL; Kamps et al, 1990;Nourse et al, 1990). The 3' portion of the PBX1 gene, including the homeobox, is fused to the 5' portion of the E2A gene, which encodes two transactivation domains.…”

Section: Introductionmentioning

confidence: 99%