The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 179K)
Right arrow Correction (v190,p1723)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gabriele, L.
Right arrow Articles by Morse, H. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gabriele, L.
Right arrow Articles by Morse, H. C., , III
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
J. Exp. Med., Volume 190, Number 3, August 2, 1999 411-422
Copyright © 1999 by The Rockefeller University Press.

Regulation of Apoptosis in Myeloid Cells by Interferon Consensus Sequence–Binding Protein

Lucia Gabrielea, Jan Phunga, Jon Fukumotoa, David Segala, I-Ming Wangb, Paraskevi Giannakakouc, Nathalie A. Giesea, Keiko Ozatob, and Herbert C. Morse, IIIa
a From The Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases
b The Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development
c The Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-0760

Correspondence to: Lucia Gabriele, LIP, NIAID, Bldg. 7, Rm. 308, 7 Center Dr., MSC 0760, NIH, Bethesda, MD 20892-0760., lgabriele{at}atlas.niaid.nih.gov (E-mail), 301-435-6525 (phone), 301-402-0077 (fax)

Mice with a null mutation of the gene encoding interferon consensus sequence–binding protein (ICSBP) develop a disease with marked expansion of granulocytes and macrophages that frequently progresses to a fatal blast crisis, thus resembling human chronic myelogenous leukemia (CML). One important feature of CML is decreased responsiveness of myeloid cells to apoptotic stimuli. Here we show that myeloid cells from mice deficient in ICSBP exhibit reduced spontaneous apoptosis and a significant decrease in sensitivity to apoptosis induced by DNA damage. In contrast, apoptosis in thymocytes from ICSBP-deficient mice is unaffected. We also show that overexpression of ICSBP in the human U937 monocytic cell line enhances the rate of spontaneous apoptosis and the sensitivity to apoptosis induced by etoposide, lipopolysaccharide plus ATP, or rapamycin. Programmed cell death induced by etoposide was specifically blocked by peptides inhibitory for the caspase-1 or caspase-3 subfamilies of caspases. Studies of proapoptotic genes showed that cells overexpressing ICSBP have enhanced expression of caspase-3 precursor protein. In addition, analyses of antiapoptotic genes showed that overexpression of ICSBP results in decreased expression of Bcl-XL. These data suggest that ICSBP modulates survival of myeloid cells by regulating expression of apoptosis-related genes.

Key Words: apoptosis, caspase, chronic myelogenous leukemia, interferon, interferon consensus sequence–binding protein


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS