These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Activation of the early growth response 1 gene and nuclear pp90rsk in human myeloid leukemia cells by 1-(beta-D-arabinofuranosyl)cytosine.
    Author: Kharbanda S, Saleem A, Rubin E, Sukhatme V, Blenis J, Kufe D.
    Journal: Biochemistry; 1993 Sep 07; 32(35):9137-42. PubMed ID: 7690249.
    Abstract:
    The early growth response 1 (EGR-1) gene is induced by mitogens, differentiating stimuli, and certain genotoxic agents in diverse cell types. The present work has examined the effects of 1-(beta-D-arabinofuranosyl)cytosine (ara-C), an antileukemia agent that misincorporates into DNA, on EGR-1 expression. Treatment of HL-525 myeloid leukemia cells with ara-C was associated with transient increases in EGR-1 mRNA levels. Nuclear run-on assays showed that this effect is related at least in part to activation of EGR-1 gene transcription. Sequences responsive to ara-C-induced signals were determined by deletion analysis of the EGR-1 promoter. The results demonstrate that ara-C inducibility of the EGR-1 gene is conferred by a region containing six serum response or CC(A/T)6GG (CArG) motifs. Further analysis demonstrated that the first two distal or 5'-most CArG elements are functional in the ara-C response. An oligomer corresponding to the first CArG element also conferred ara-C inducibility of the minimal thymdine kinase gene promoter, while no inducibility was detectable using a similar oligomer containing a mutated CArG box. Other work has demonstrated that the nuclear serum response factor (SRF) interacts with the CArG box in the EGR-1 promoter and that the serine/threonine pp90rsk protein kinase phosphorylates SRF in vitro at sites phosphorylated in vivo. The present studies demonstrate that ara-C has little if any effect on cytosolic pp90rsk as determined by immunoblotting to assess electrophoretic mobility and by immune-complex kinase assays using S6 peptide as substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
    [Abstract] [Full Text] [Related] [New Search]