WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis

Wafik S. El-Deiry, Victor E Velculescu, Patrick M. O'Connor, Victor E. Velculescu, Christine E. Canman, Kenneth W Kinzler, Bert Vogelstein, Marilee Burrell, David E. Hill, Yisong Wang, Klas G. Wiman, W. Edward Mercer, Michael B. Kastan, Kurt W. Kohn, Stephen J. Elledge, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

The tumor growth suppressor WAF1/CIP1 was recently shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing wild-type p53 and undergoing G1 arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G1 arrest or apoptosis but not in cells induced to arrest in G1 or to undergo apoptosis through p53-independent mechanisms. DNA damage led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53- specific pathway of growth control in mammalian cells.

Original languageEnglish (US)
Pages (from-to)1169-1174
Number of pages6
JournalCancer Research
Volume54
Issue number5
StatePublished - Mar 1 1994

Fingerprint

Apoptosis
Cyclin-Dependent Kinases
Cyclin E
Growth
Cell Nucleus
DNA Damage
Proteins
DNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

El-Deiry, W. S., Velculescu, V. E., O'Connor, P. M., Velculescu, V. E., Canman, C. E., Kinzler, K. W., ... Vogelstein, B. (1994). WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Research, 54(5), 1169-1174.

WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. / El-Deiry, Wafik S.; Velculescu, Victor E; O'Connor, Patrick M.; Velculescu, Victor E.; Canman, Christine E.; Kinzler, Kenneth W; Vogelstein, Bert; Burrell, Marilee; Hill, David E.; Wang, Yisong; Wiman, Klas G.; Mercer, W. Edward; Kastan, Michael B.; Kohn, Kurt W.; Elledge, Stephen J.; Kinzler, Kenneth W.; Vogelstein, Bert.

In: Cancer Research, Vol. 54, No. 5, 01.03.1994, p. 1169-1174.

Research output: Contribution to journalArticle

El-Deiry, WS, Velculescu, VE, O'Connor, PM, Velculescu, VE, Canman, CE, Kinzler, KW, Vogelstein, B, Burrell, M, Hill, DE, Wang, Y, Wiman, KG, Mercer, WE, Kastan, MB, Kohn, KW, Elledge, SJ, Kinzler, KW & Vogelstein, B 1994, 'WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis', Cancer Research, vol. 54, no. 5, pp. 1169-1174.
El-Deiry WS, Velculescu VE, O'Connor PM, Velculescu VE, Canman CE, Kinzler KW et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Research. 1994 Mar 1;54(5):1169-1174.
El-Deiry, Wafik S. ; Velculescu, Victor E ; O'Connor, Patrick M. ; Velculescu, Victor E. ; Canman, Christine E. ; Kinzler, Kenneth W ; Vogelstein, Bert ; Burrell, Marilee ; Hill, David E. ; Wang, Yisong ; Wiman, Klas G. ; Mercer, W. Edward ; Kastan, Michael B. ; Kohn, Kurt W. ; Elledge, Stephen J. ; Kinzler, Kenneth W. ; Vogelstein, Bert. / WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. In: Cancer Research. 1994 ; Vol. 54, No. 5. pp. 1169-1174.
@article{0edc066724ff4438826d62ffbb8ae1a0,
title = "WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis",
abstract = "The tumor growth suppressor WAF1/CIP1 was recently shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing wild-type p53 and undergoing G1 arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G1 arrest or apoptosis but not in cells induced to arrest in G1 or to undergo apoptosis through p53-independent mechanisms. DNA damage led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53- specific pathway of growth control in mammalian cells.",
author = "El-Deiry, {Wafik S.} and Velculescu, {Victor E} and O'Connor, {Patrick M.} and Velculescu, {Victor E.} and Canman, {Christine E.} and Kinzler, {Kenneth W} and Bert Vogelstein and Marilee Burrell and Hill, {David E.} and Yisong Wang and Wiman, {Klas G.} and Mercer, {W. Edward} and Kastan, {Michael B.} and Kohn, {Kurt W.} and Elledge, {Stephen J.} and Kinzler, {Kenneth W.} and Bert Vogelstein",
year = "1994",
month = "3",
day = "1",
language = "English (US)",
volume = "54",
pages = "1169--1174",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis

AU - El-Deiry, Wafik S.

AU - Velculescu, Victor E

AU - O'Connor, Patrick M.

AU - Velculescu, Victor E.

AU - Canman, Christine E.

AU - Kinzler, Kenneth W

AU - Vogelstein, Bert

AU - Burrell, Marilee

AU - Hill, David E.

AU - Wang, Yisong

AU - Wiman, Klas G.

AU - Mercer, W. Edward

AU - Kastan, Michael B.

AU - Kohn, Kurt W.

AU - Elledge, Stephen J.

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

PY - 1994/3/1

Y1 - 1994/3/1

N2 - The tumor growth suppressor WAF1/CIP1 was recently shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing wild-type p53 and undergoing G1 arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G1 arrest or apoptosis but not in cells induced to arrest in G1 or to undergo apoptosis through p53-independent mechanisms. DNA damage led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53- specific pathway of growth control in mammalian cells.

AB - The tumor growth suppressor WAF1/CIP1 was recently shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinases. In the present studies, we sought to determine the relationship between the expression of WAF1/CIP1 and endogenous regulation of p53 function. WAF1/CIP1 protein was first localized to the nucleus of cells containing wild-type p53 and undergoing G1 arrest. WAF1/CIP1 was induced in wild-type p53-containing cells by exposure to DNA damaging agents, but not in mutant p53-containing cells. The induction of WAF1/CIP1 protein occurred in cells undergoing either p53-associated G1 arrest or apoptosis but not in cells induced to arrest in G1 or to undergo apoptosis through p53-independent mechanisms. DNA damage led to increased levels of WAF1/CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. These results support the idea that WAF1/CIP1 is a critical downstream effector in the p53- specific pathway of growth control in mammalian cells.

UR - http://www.scopus.com/inward/record.url?scp=0028294605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028294605&partnerID=8YFLogxK

M3 - Article

C2 - 8118801

AN - SCOPUS:0028294605

VL - 54

SP - 1169

EP - 1174

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 5

ER -