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(Circulation Research. 2001;88:262.)
© 2001 American Heart Association, Inc.

Editorial

Nuclear Factor-B and Cell Survival

IAPs Call for Support

Richard T. Lee, Tucker Collins

From the Cardiovascular Division (R.T.L.), Department of Medicine, and the Vascular Research Division (T.C.), Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Richard T. Lee, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail rlee@rics.bwh.harvard.edu

Key Words: apoptosis • cell survival • caspases • cell cycle

	Introduction

 
Programmed cellular death can occur in all cells by highly efficient mechanisms, leading to the quiet disposal of millions of cells in the adult human each minute. This efficient execution of unwanted cells is regulated not only by cellular death signals but also by cellular survival signals. Imbalances in these signals are lethal in the development of higher organisms and likely play a major role in pathophysiological processes as diverse as atherosclerosis, cancer, heart failure, and inflammation.

As a ubiquitous multifunctional signaling system, members of the nuclear factor-B (NF-B) family play prominent roles in the cell death/survival balance.¹ NF-B proteins are homodimers or heterodimers in the cytoplasm of eukaryotic cells that share a 300 amino acid motif called the REL homology domain.² The REL homology domain mediates dimer formation, nuclear localization, and interaction with inhibitory proteins (IB proteins) that keep NF-B proteins in the cytoplasm. Diverse cellular stimuli including mechanical forces, oxidative stress, and cytokines lead to phosphorylation of IB proteins, allowing NF-B dimers to enter the nucleus and activate specific target genes.

Under many circumstances, activation of NF-B complexes is a powerful stimulus for cell survival (Figure). For example, in B lymphocytes, the cell type in which NF-B was originally identified, engagement of cell surface IgM activates NF-B and inhibits apoptosis.³ In addition, mice lacking RelA, one of the NF-B family members, die at embryonic development day 10 of massive hepatic apoptosis.⁴ However, NF-B activation does . . . [Full Text of this Article]

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