P53-independent activation of transcription of p21waf1/cip1/sdi1
after acute renal failure.
Megyesi, Judit, Nora Udvarhelyi, Robert L. Safirstein, and Peter M.
Price.
Department of Medicine, Division of Nephrology and Sealy Center for
Molecular Science, University of Texas Medical Branch, Galveston, TX
77555
APStracts 3:0159F, 1996.
In three different models of acute renal failure (ischemia, ureteral
obstruction, and cisplatin administration), the p21WAF1/CIP1/SDI1
gene, whose protein product is associated with cell-cycle
interruption, terminal differentiation, and cellular senescence, was
activated in murine kidney cells. This transcription was localized in
kidney only to cells of thick ascending limbs and distal convoluted
tubules. Although the tumor suppressor protein, p53, can trans
-activate the p21 gene in some cells, increased levels of nuclear p53
protein could be demonstrated only in the cisplatin model of acute
renal failure. High levels of p21 mRNA were induced in kidney of p53
"null" mice, demonstrating that p21 gene activation was
through a p53-independent pathway. We also present evidence that in
the cisplatin model, both p53-independent and p53-dependent induction
of p21 mRNA occurs simultaneously. We conclude that p21 gene
activation is a general response to renal injury and could be a key
determinant of cell fate in the cell in which it is expressed.
Received 28 June 1996; accepted in final form 29 August 1996.
APS Manuscript Number F180-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996