p21Waf1/Cip1/Sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in recovering cells

被引：153

作者：

Chang, BD ^{[1
]}

Broude, EV ^{[1
]}

Fang, J ^{[1
]}

Kalinichenko, TV ^{[1
]}

Abdryashitov, R ^{[1
]}

Poole, JC ^{[1
]}

Roninson, IB ^{[1
]}

机构：

[1] Univ Illinois, Dept Mol Genet MC 669, Chicago, IL 60607 USA

来源：

ONCOGENE | 2000年 / 19卷 / 17期

关键词：

p21; mitosis; endoreduplication; spindle checkpoint control; senescence;

D O I：

10.1038/sj.onc.1203573

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Induction of a cyclin-dependent kinase inhibitor p21(Wafl/) (Cip1/Sdi1) is an integral part of cell growth arrest associated with senescence and damage response, p21 overexpression from an inducible promoter resulted in senescence-like growth arrest in a human fibrosarcoma cell line. After release from p21-induced growth arrest, cells reentered the cell cycle but displayed growth retardation, cell death and decreased clonogenicity. The failure to form colonies was associated with abnormal mitosis and endoreduplication in the recovering cells and was correlated with the induced level of p21 and the duration of p21 induction. p21 induction was found to inhibit the expression of multiple proteins involved in the execution and control of mitosis, p21-induced depletion of the cellular pools of mitosis-control proteins nas followed by asynchronous resynthesis of such proteins after release from p21, which explains the observed mitotic abnormalities. Genetic destabilization in cells recovering from p21-induced growth arrest may conceivably play a role in carcinogenesis and tumor progression.

引用

页码：2165 / 2170

页数：6

共 41 条

[1]

Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts [J].

Alcorta, DA ;

Xiong, Y ;

Phelps, D ;

Hannon, G ;

Beach, D ;

Barrett, JC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :13742-13747

[2]

Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression [J].

Bates, S ;

Ryan, KM ;

Phillips, AC ;

Vousden, KH .

ONCOGENE, 1998, 17 (13) :1691-1703

[3]

Requirement for p53 and p21 to sustain G2 arrest after DNA damage [J].

Bunz, F ;

Dutriaux, A ;

Lengauer, C ;

Waldman, T ;

Zhou, S ;

Brown, JP ;

Sedivy, JM ;

Kinzler, KW ;

Vogelstein, B .

SCIENCE, 1998, 282 (5393) :1497-1501

[4]

Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC [J].

Chan, GKT ;

Jablonski, SA ;

Sudakin, V ;

Hittle, JC ;

Yen, TJ .

JOURNAL OF CELL BIOLOGY, 1999, 146 (05) :941-954

[5]

Chang BD, 1999, CANCER RES, V59, P3761

[6]

Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs [J].

Chang, BD ;

Xuan, YZ ;

Broude, EV ;

Zhu, HM ;

Schott, B ;

Fang, J ;

Roninson, IB .

ONCOGENE, 1999, 18 (34) :4808-4818

[7]

CHANG BD, 1999, CANCER RES, V18, P4808

[8]

CHANG BP, 2000, IN PRESS P NATL ACAD

[9]

MICE LACKING P21(C/P1/WAF1) UNDERGO NORMAL DEVELOPMENT, BUT ARE DEFECTIVE IN G1 CHECKPOINT CONTROL [J].

DENG, CX ;

ZHANG, PM ;

HARPER, JW ;

ELLEDGE, SJ ;

LEDER, P .

CELL, 1995, 82 (04) :675-684

[10]

DNA-DAMAGE TRIGGERS A PROLONGED P53-DEPENDENT G(1) ARREST AND LONG-TERM INDUCTION OF CIP1 IN NORMAL HUMAN FIBROBLASTS [J].

DI LEONARDO, A ;

LINKE, SP ;

CLARKIN, K ;

WAHL, GM .

GENES & DEVELOPMENT, 1994, 8 (21) :2540-2551

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