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(Circulation Research. 2002;91:4.)
© 2002 American Heart Association, Inc.

Editorials

Hypoxia and HIF-1 Stability

Another Stress-Sensing Mechanism for Shc

Jun-ichi Abe, Bradford C. Berk

From the Center for Cardiovascular Research, University of Rochester, Rochester, NY.

Correspondence to Bradford C. Berk, MD, PhD, Cardiology Unit, Box 679, 601 Elmwood Ave, Rochester, NY 14642. E-mail Bradford_Berk@urmc.rochester.edu

Key Words: signal transduction • Shc • hypoxia-inducible factor-1 • hypoxia

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The formation of new blood vessels after ischemia and vascular injury is a critical process for tissue repair. A complex interplay of stress-activated signal transduction pathways is activated in response to ischemia and injury to initiate the repair process. Among these pathways, the hypoxia-inducible transcription factor-1 (HIF-1) plays an essential role by transactivating the VEGF gene and activating a pattern of gene expression associated with mobilization, migration, and recruitment of endothelial cells and smooth muscle cells to form new blood vessels.^1–3 The report by Jung et al⁴ in this issue of Circulation Research investigates the signaling pathway responsible for hypoxia-induced HIF-1 protein stabilization and concludes that a mechanism involving Src, Shc, Ras, and Raf-1 is critical in endothelial cells.

In this editorial, we discuss 5 key issues raised by the work of Jung et al.⁴ (1) Signal transduction pathways that regulate protein stabilization are important pathophysiological mechanisms that may provide novel therapeutic approaches. (2) Shc isoforms represent a family of stress-regulated proteins that act as sensors for redox, oxygen species (ROS), and other genotoxic stresses. (3) Shc proteins mediate signal transduction in localized subcellular compartments, which are likely essential for hypoxia signaling pathways. (4) Cell migration in response to hypoxia likely involves multiple mechanisms including Shc. (5) Dominant-negative (DN) proteins represent an important technical advance to define signal transduction pathways, but appropriate controls must be used to avoid nonspecific effects.

Structure of Shc Isoforms and Grb2/Sos/Ras

Shc is an adaptor protein that possesses no intrinsic enzymatic activity, yet alterations in its structure have profound functional . . . [Full Text of this Article]

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