Document 0064
 DOCN  M95B0064
 TI    Nucleolar localization of parathyroid hormone-related peptide enhances
       survival of chondrocytes under conditions that promote apoptotic cell
       death.
 DT    9511
 AU    Henderson JE; Amizuka N; Warshawsky H; Biasotto D; Lanske BM; Goltzman
       D; Karaplis AC; Division of Endocrinology, Sir Mortimer B. Davis-Jewish
       General; Hospital, Montreal, Quebec, Canada.
 SO    Mol Cell Biol. 1995 Aug;15(8):4064-75. Unique Identifier : AIDSLINE
       MED/95349572
 AB    Parathyroid hormone-related peptide (PTHrP) is a mediator of cellular
       growth and differentiation as well as a cause of malignancy-induced
       hypercalcemia. Most of the actions of PTHrP have been attributed to its
       interaction with a specific cell surface receptor that binds the
       N-terminal domain of the protein. Here we present evidence that PTHrP
       promotes some of its cellular effects by translocating to the nucleolus.
       Localization of transiently expressed PTHrP to the nucleolus was
       dependent on the presence of a highly basic region at the carboxyl
       terminus of the molecule that bears homology to nucleolar targeting
       sequences identified within human retroviral (human immunodeficiency
       virus type 1 and human T-cell leukemia virus type 1) regulatory
       proteins. Endogenous PTHrP also localized to the nucleolus in osseous
       cells in vitro and in vivo. Moreover, expression of PTHrP in
       chondrocytic cells (CFK2) delayed apoptosis induced by serum
       deprivation, and this effect depended on the presence of an intact
       nucleolar targeting signal. The present findings demonstrate a unique
       intracellular mode of PTHrP action and a novel mechanism by which this
       peptide growth factor may modulate programmed cell death.
 DE    Amino Acid Sequence  Apoptosis  Base Sequence  Biological Transport
       Cartilage/CYTOLOGY/*PHYSIOLOGY  *Cell Compartmentation  Cell
       Nucleolus/*METABOLISM  Cell Survival  DNA Damage  Immunohistochemistry
       Molecular Sequence Data  Parathyroid Hormones/GENETICS/*METABOLISM
       Peptide Fragments/GENETICS/METABOLISM  Precipitin Tests
       Proteins/GENETICS/*METABOLISM  Recombinant Proteins/METABOLISM  Signal
       Transduction  Structure-Activity Relationship  Support, Non-U.S. Gov't
       Transfection  Translation, Genetic  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).