Perspective

ESCRT proteins: Double-edged regulators of cellular signaling

Volume 1, Issue 1   January/February 2011
Pages 45 - 48
http://dx.doi.org/10.4161/bioa.1.1.15173
Authors: Chun Tu, Gulzar Ahmad, Bhopal Mohapatra, Sohinee Bhattacharyya, Cesar Ortega-Cava, Byung Min Chung, Kay-Uwe Wagner, Srikumar M. Raja, Mayumi Naramura, Vimla Band and Hamid Band

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Abstract:
ESCRT pathway proteins play a key role in sorting ubiquitinated membrane receptors towards lysosomes providing an important mechanism for attenuating cell surface receptor signaling. However, recent studies point to a positive role of ESCRT proteins in signal transduction in multiple species studied under physiological and pathological conditions. ESCRT components such as Tsg101 and Hrs are overexpressed in human cancers and Tsg101 depletion is detrimental for cell proliferation, survival, and transformed phenotype of tumor cells. However, the mechanisms underlying the positive contributions of ESCRT pathway to surface receptor signaling have remained unclear. In a recent study, we showed that Tsg101 and Vps4 are essential for translocation of active Src from endosomes to focal adhesion and invadopodia, thereby revealing a role of ESCRT pathway in promoting Src-mediated migration and invasion. We discuss the implications of these and other recent studies which together suggest a role for the ESCRT pathway in recycling of endocytic cargo proteins, aside from its role in lysosomal targeting, potentially explaining the positive roles of ESCRT proteins in signal transduction.

Perspective to:
C Tu, CF Ortega-Cava, P Winograd, MJ Stanton, AL Reddi, I Dodge, R Arya, M Dimri, RJ Clubb, M Naramura, KU Wagner, V Band, H Band. Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active Src at focal adhesions. Proc Natl Acad Sci U S A 2010; 107: 16107-12
PMID: 20805499

Received: February 13, 2011; Accepted: February 15, 2011

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