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Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein.
Oncogene. 1993 Aug; 8(8):2167-73.O

Abstract

Three of the ets oncogene superfamily members v-ets, Spi-1/PU.1 and Fli-1, have been shown to be directly involved in retroviral-mediated acute erythroleukemias. The Fli-1 gene was found to be rearranged in 75% of the erythroleukemias induced by Friend murine leukemia virus (F-MuLV), suggesting that it could play a key role in cellular transformation. We have previously isolated and characterized the human Fli-1 gene and have found it to be highly homologous (80%) to the human erg-2 gene. Human Fli-1 was also shown to be rearranged in Ewing's sarcoma cases, in which the amino-terminal region of the Fli-1 gene was replaced with a novel coding region of a putative RNA-binding protein, EWS. In this report, we show that the recombinant Fli-1 protein expressed in bacteria binds to DNA in a sequence-specific manner. It appears that Fli-1 and erg proteins fall into the category of ets proteins that recognize limited ets target sequences, unlike c-ets-1, ets-2 and Elk-1. The Fli-1 gene was found to activate the transcription of the reporter gene that was linked to Fli-1 target sequences, suggesting that Fli-1 is a sequence-specific transcriptional activator. Deletion analysis revealed the presence of two autonomous transcriptional activation domains, one at the amino-terminal region (amino-terminal transcriptional activation domain, ATA) and the other at the carboxy-terminal region (carboxy-terminal transcriptional activation domain, CTA). Secondary structural analysis of ATA and CTA domains revealed the presence of helix-loop-helix (H-L-H) and/or turn-loop-turn (T-L-T) regions. From these results it appears that a portion of the Fli-1 ATA domain (H-L-H region) was replaced by the amino-terminal domain of EWS gene in Ewing's sarcoma cases. Therefore alteration in the transcriptional activation function of Fli-1 may be responsible for human malignancies such as sarcomas, leukemias and lymphomas in which this gene is rearranged.

Authors+Show Affiliations

Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8336942

Citation

Rao, V N., et al. "Analysis of the DNA-binding and Transcriptional Activation Functions of Human Fli-1 Protein." Oncogene, vol. 8, no. 8, 1993, pp. 2167-73.
Rao VN, Ohno T, Prasad DD, et al. Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein. Oncogene. 1993;8(8):2167-73.
Rao, V. N., Ohno, T., Prasad, D. D., Bhattacharya, G., & Reddy, E. S. (1993). Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein. Oncogene, 8(8), 2167-73.
Rao VN, et al. Analysis of the DNA-binding and Transcriptional Activation Functions of Human Fli-1 Protein. Oncogene. 1993;8(8):2167-73. PubMed PMID: 8336942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of the DNA-binding and transcriptional activation functions of human Fli-1 protein. AU - Rao,V N, AU - Ohno,T, AU - Prasad,D D, AU - Bhattacharya,G, AU - Reddy,E S, PY - 1993/8/1/pubmed PY - 1993/8/1/medline PY - 1993/8/1/entrez SP - 2167 EP - 73 JF - Oncogene JO - Oncogene VL - 8 IS - 8 N2 - Three of the ets oncogene superfamily members v-ets, Spi-1/PU.1 and Fli-1, have been shown to be directly involved in retroviral-mediated acute erythroleukemias. The Fli-1 gene was found to be rearranged in 75% of the erythroleukemias induced by Friend murine leukemia virus (F-MuLV), suggesting that it could play a key role in cellular transformation. We have previously isolated and characterized the human Fli-1 gene and have found it to be highly homologous (80%) to the human erg-2 gene. Human Fli-1 was also shown to be rearranged in Ewing's sarcoma cases, in which the amino-terminal region of the Fli-1 gene was replaced with a novel coding region of a putative RNA-binding protein, EWS. In this report, we show that the recombinant Fli-1 protein expressed in bacteria binds to DNA in a sequence-specific manner. It appears that Fli-1 and erg proteins fall into the category of ets proteins that recognize limited ets target sequences, unlike c-ets-1, ets-2 and Elk-1. The Fli-1 gene was found to activate the transcription of the reporter gene that was linked to Fli-1 target sequences, suggesting that Fli-1 is a sequence-specific transcriptional activator. Deletion analysis revealed the presence of two autonomous transcriptional activation domains, one at the amino-terminal region (amino-terminal transcriptional activation domain, ATA) and the other at the carboxy-terminal region (carboxy-terminal transcriptional activation domain, CTA). Secondary structural analysis of ATA and CTA domains revealed the presence of helix-loop-helix (H-L-H) and/or turn-loop-turn (T-L-T) regions. From these results it appears that a portion of the Fli-1 ATA domain (H-L-H region) was replaced by the amino-terminal domain of EWS gene in Ewing's sarcoma cases. Therefore alteration in the transcriptional activation function of Fli-1 may be responsible for human malignancies such as sarcomas, leukemias and lymphomas in which this gene is rearranged. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/8336942/Analysis_of_the_DNA_binding_and_transcriptional_activation_functions_of_human_Fli_1_protein_ L2 - https://antibodies.cancer.gov/detail/CPTC-ATM-4 DB - PRIME DP - Unbound Medicine ER -