Characterization of the Promoter Region of the Human C-kit Proto-oncogene

Overview

Journal Jpn J Cancer Res

Specialty Oncology

Date 1993 Nov 1

PMID 7506248

Citations 27

Authors

K Yamamoto

A Tojo

N Aoki

M Shibuya

Affiliations

Soon will be listed here.

Abstract

The c-kit proto-oncogene encodes a tyrosine kinase receptor for stem cell factor and plays a critical role in the growth and differentiation of various types of cells including hematopoietic stem cells. To investigate the mechanisms of its transcriptional regulation, we isolated the 5' flanking region of the human c-kit gene and characterized its promoter activity in hematopoietic cells. Nucleotide sequence analysis revealed that the 1.2 kb 5' flanking region lacked a typical "TATA box," but had a relatively high G + C content and four potential Sp1-binding sites. Putative binding sites for AP-2, basic helix-loop-helix proteins, Ets-domain proteins, Myb and GATA-1 were also found. Primer extension and S1 nuclease protection analyses of hematopoietic cells indicated that the major transcription start sites are 62 bp and 58 bp upstream of the translation start site. Essentially the same start sites were detected in non-hematopoietic cells such as small cell lung carcinoma and glioblastoma: this single promoter in c-kit is different from the multiple promoter system of c-fms, a c-kit-related gene, in which at least two promoters are differently used in hematopoietic and non-hematopoietic cells. An analysis of the c-kit 5' flanking region using the bacterial chloramphenicol acetyltransferase gene (CAT assay) in human erythroleukemia HEL cells, which express the endogenous c-kit mRNA at high levels, showed that a region from -180 to -22 is important for the expression of the c-kit gene. In addition, a negative regulatory element(s) is suggested to be involved in the regulation of the c-kit gene expression in mammals.

Citing Articles

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A novel anti-c-Kit antibody-drug conjugate to treat wild-type and activating-mutant c-Kit-positive tumors.

Kim J, Kim K, Baek E, Park B, So M, Ko B Mol Oncol. 2021; 16(6):1290-1308.

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c-kit2 G-quadruplex stabilized via a covalent probe: exploring G-quartet asymmetry.

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G-Quadruplex Modulation of SP1 Functional Binding Sites at the Proximal Promoter.

Da Ros S, Nicoletto G, Rigo R, Ceschi S, Zorzan E, Dacasto M Int J Mol Sci. 2021; 22(1).

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Polarizable Molecular Dynamics Simulations of Two Oncogene Promoter G-Quadruplexes: Effect of Primary and Secondary Structure on Loop and Ion Sampling.

Salsbury A, Dean T, Lemkul J J Chem Theory Comput. 2020; 16(5):3430-3444.

PMID: 32307997 PMC: 7221321. DOI: 10.1021/acs.jctc.0c00191.

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