ROLE OF ACTIN CYTOSKELETON ON UVA INDUCED APOPTOSIS

  • Slaughter, Clive A. (PI)
  • YIN, HELEN (PI)
  • MATSUE, HIROYUKI (PI)
  • GRAFF, JONATHAN (PI)
  • SCHULTZ, ROGER (PI)
  • LERNER, MICHAEL (PI)
  • SATO, NARUTOKU (PI)
  • TAKASHIMA, AKIRA (PI)
  • BERGSTRESSER, PAUL (PI)
  • Bennett, Michael (PI)

Project: Research project

Project Details

Description

Apoptosis occurs under a variety of physiological and pathological
conditions. It is essential for maintaining the homeostasis of the
skin, and inappropriate apoptosis has been implicated in the
pathogenesis of a multitude of skin disorders. Apoptosis mediates the
decrease in cellularity during the transition between granulation to
scar tissue, and aberrant apoptosis during wound healing has been
attributed to the development of hypertrophic scars and keloids.
Apoptosis may protect against the development of UV-induced skin cancer
by selectively destroying sun-damaged keratinocytes. Mutations in the
components of the surveillance machinery, such as p53 and bd-2, provide
cells with an opportunity to escape from apoptosis and develop into
nonmelanoma skin cancers. Early onset of apoptosis has been observed
in diabetic wounds, contributing to blunted wound healing. Thus,
manipulations which alter the onset or extent of apoptosis can
potentially provide therapeutic interventions for the treatment of a
variety of skin diseases. It is therefore important to delineate the
molecular pathways and regulation of this multistep process. In this
grant, I propose to use a variety of ways to manipulate the actin
cytoskeleton and determine how actin remodeling contributes to UV-
induced apoptosis in keratinocytes. I will examine the role of
gelsolin, a Ca2+-activated actin filament severing protein which is
recently identified as a direct and predominant substrate of caspase-3,
in UVB-mediated apoptosis. This project is a new direction for my
laboratory, but is very appropriate and timely because very little is
known about the involvement of the actin cytoskeleton in apoptosis,
even though the cytoskeleton is an important structural and regulatory
machine. Its derangement is likely to contribute to the
pathophysiological of many skin diseases. We have the tools and
expertise to investigate this very important basic biological problem,
and anticipate that our findings will suggest novel approaches for the
treatment/or prevention of many skin diseases.
StatusNot started