Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells.
Open Access
- 1 March 1994
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 14 (3), 1845-1851
- https://doi.org/10.1128/mcb.14.3.1845
Abstract
We have previously shown that the signal peptideless cytokine interleukin 1 alpha (IL-1 alpha) may play a role as an intracellular regulator of human endothelial cell senescence (J. A. M. Maier, P. Voulalas, D. Roeder, and T. Maciag, Science 249:1570-1574, 1990). To investigate the potential intracellular function of IL-1 alpha, transformed endothelial cells were transfected with the human cDNAs that code for the two forms of IL-1 alpha, the precursor molecule IL-1(1-271) and the mature protein IL-1(113-271). The subcellular localization of the two different polypeptides was investigated directly or by using chimeric genes constructed by fusion of different fragments of the IL-1 alpha gene and the beta-galactosidase open reading frames. The IL-1(113-271) protein was cytoplasmic, while IL-1(1-271) was nuclear. The basic cluster at the NH2 terminus of IL-1, KVLKKRR, has been shown to mediate IL-1 alpha nuclear targeting. Moreover, nuclear localization of IL-1 alpha correlates with impaired cell growth and expression of some IL-1 alpha-inducible genes. These results suggest that transport of endogenous IL-1(1-271) into the nucleus is required for it to modulate endothelial cell function.Keywords
This publication has 46 references indexed in Scilit:
- Differential Expression of the Common β and Specific α Chains of the Receptors for GM-CSF, IL-3, and IL-5 in Endothelial CellsExperimental Cell Research, 1993
- Interleukin‐1α gene expression and localization of interleukin‐1α protein during tumor promotionMolecular Carcinogenesis, 1993
- Analysis of endogenous and exogenous nuclear translocation of fibroblast growth factor-1 in NIH 3T3 cellsBiochemical and Biophysical Research Communications, 1992
- Nuclear import-export: In search of signals and mechanismsCell, 1991
- Extension of the Life-Span of Human Endothelial Cells by an Interleukin-1αAntisense OligomerScience, 1990
- Human interleukin 1 beta is not secreted from hamster fibroblasts when expressed constitutively from a transfected cDNA.The Journal of cell biology, 1988
- Acid blobs and negative noodlesNature, 1988
- Interleukin 1 beta is localized in the cytoplasmic ground substance but is largely absent from the Golgi apparatus and plasma membranes of stimulated human monocytes.The Journal of Experimental Medicine, 1988
- Angiogenic FactorsScience, 1987
- Organizational behavior of human umbilical vein endothelial cells.The Journal of cell biology, 1982