The Role of Cdc25A in the Regulation of Cell Proliferation and Apoptosis

Overview

Journal Anticancer Agents Med Chem

Publisher Bentham Science Publishers

Specialties Chemistry
Oncology

Date 2012 Jan 24

PMID 22263797

Citations 104

Authors

Tao Shen

Shile Huang

Affiliations

Soon will be listed here.

Abstract

Cell division cycle 25 A (Cdc25A), a dual-specificity protein phosphatase, is one of the most crucial cell cycle regulators, which removes the inhibitory phosphorylation in cyclin-dependent kinases (CDKs), such as CDK2, CDK4, and CDK6, and positively regulates the activities of CDKs that lead to cell cycle progression. In addition, Cdc25A also acts as a regulator of apoptosis. Overexpression of Cdc25A promotes tumorigenesis, and is frequently observed in various types of cancer. Here we briefly summarize current understanding of the role of Cdc25A in cell proliferation and apoptosis, as well as the impact of overexpression of Cdc25A on tumorigenesis.

Citing Articles

Endophytic Fungal Diversity and Its Interaction Mechanism with Medicinal Plants.

Gao Y, Xu Y, Dong Z, Guo Y, Luo J, Wang F Molecules. 2025; 30(5).

PMID: 40076252 PMC: 11902086. DOI: 10.3390/molecules30051028.

Identifying Essential Hub Genes and circRNA-Regulated ceRNA Networks in Hepatocellular Carcinoma.

Yu X, Xu H, Xing Y, Sun D, Li D, Shi J Int J Mol Sci. 2025; 26(4).

PMID: 40003874 PMC: 11855757. DOI: 10.3390/ijms26041408.

TDP-43/ALKBH5-mediated mA modification of CDC25A mRNA promotes glioblastoma growth by facilitating G1/S cell cycle transition.

Zhang Y, Xie S, Li W, Gu J, Zhang X, Ni B MedComm (2020). 2025; 6(3):e70108.

PMID: 39974663 PMC: 11836349. DOI: 10.1002/mco2.70108.

DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance.

Gupta S, Silveira D, Mombach J, Hashimoto R Proteomes. 2025; 13(1.

PMID: 39846637 PMC: 11755436. DOI: 10.3390/proteomes13010006.

Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.

Pellarin I, DallAcqua A, Favero A, Segatto I, Rossi V, Crestan N Signal Transduct Target Ther. 2025; 10(1):11.

PMID: 39800748 PMC: 11734941. DOI: 10.1038/s41392-024-02080-z.

References

Ray D, Kiyokawa H . CDC25A phosphatase: a rate-limiting oncogene that determines genomic stability. Cancer Res. 2008; 68(5):1251-3. DOI: 10.1158/0008-5472.CAN-07-5983. View

Cangi M, Cukor B, Soung P, Signoretti S, Moreira Jr G, Ranashinge M . Role of the Cdc25A phosphatase in human breast cancer. J Clin Invest. 2000; 106(6):753-61. PMC: 381390. DOI: 10.1172/JCI9174. View

Takeda K, Noguchi T, Naguro I, Ichijo H . Apoptosis signal-regulating kinase 1 in stress and immune response. Annu Rev Pharmacol Toxicol. 2007; 48:199-225. DOI: 10.1146/annurev.pharmtox.48.113006.094606. View

Ray D, Terao Y, Fuhrken P, Ma Z, DeMayo F, Christov K . Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability. Cancer Res. 2007; 67(3):984-91. DOI: 10.1158/0008-5472.CAN-06-3927. View

Behrens A, Sibilia M, Wagner E . Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat Genet. 1999; 21(3):326-9. DOI: 10.1038/6854. View

Lundberg A, Weinberg R . Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol. 1998; 18(2):753-61. PMC: 108786. DOI: 10.1128/MCB.18.2.753. View

Dong J, Peng J, Zhang H, Mondesire W, Jian W, Mills G . Role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity. Cancer Res. 2005; 65(5):1961-72. DOI: 10.1158/0008-5472.CAN-04-2501. View

Demidova A, Aau M, Zhuang L, Yu Q . Dual regulation of Cdc25A by Chk1 and p53-ATF3 in DNA replication checkpoint control. J Biol Chem. 2008; 284(7):4132-9. DOI: 10.1074/jbc.M808118200. View

Wang P, Zou F, Zhang X, Li H, Dulak A, Tomko Jr R . microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 2009; 69(20):8157-65. PMC: 2763324. DOI: 10.1158/0008-5472.CAN-09-1996. View

10.

MacDonald K, Bennett M . cdc25A is necessary but not sufficient for optimal c-myc-induced apoptosis and cell proliferation of vascular smooth muscle cells. Circ Res. 1999; 84(7):820-30. DOI: 10.1161/01.res.84.7.820. View

11.

Loffler H, Syljuasen R, Bartkova J, Worm J, Lukas J, Bartek J . Distinct modes of deregulation of the proto-oncogenic Cdc25A phosphatase in human breast cancer cell lines. Oncogene. 2003; 22(50):8063-71. DOI: 10.1038/sj.onc.1206976. View

12.

Martinez-Balbas M, Bauer U, Nielsen S, Brehm A, Kouzarides T . Regulation of E2F1 activity by acetylation. EMBO J. 2000; 19(4):662-71. PMC: 305604. DOI: 10.1093/emboj/19.4.662. View

13.

Leppa S, Bohmann D . Diverse functions of JNK signaling and c-Jun in stress response and apoptosis. Oncogene. 1999; 18(45):6158-62. DOI: 10.1038/sj.onc.1203173. View

14.

Bartek J, Lukas J . Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr Opin Cell Biol. 2001; 13(6):738-47. DOI: 10.1016/s0955-0674(00)00280-5. View

15.

Uto K, Inoue D, Shimuta K, Nakajo N, Sagata N . Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism. EMBO J. 2004; 23(16):3386-96. PMC: 514503. DOI: 10.1038/sj.emboj.7600328. View

16.

Resnitzky D, Reed S . Different roles for cyclins D1 and E in regulation of the G1-to-S transition. Mol Cell Biol. 1995; 15(7):3463-9. PMC: 230582. DOI: 10.1128/MCB.15.7.3463. View

17.

Uchino S, Noguchi M, Ochiai A, Saito T, Kobayashi M, Hirohashi S . p53 mutation in gastric cancer: a genetic model for carcinogenesis is common to gastric and colorectal cancer. Int J Cancer. 1993; 54(5):759-64. DOI: 10.1002/ijc.2910540509. View

18.

Kasahara K, Goto H, Enomoto M, Tomono Y, Kiyono T, Inagaki M . 14-3-3gamma mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage. EMBO J. 2010; 29(16):2802-12. PMC: 2924644. DOI: 10.1038/emboj.2010.157. View

19.

Rudolph J . Cdc25 phosphatases: structure, specificity, and mechanism. Biochemistry. 2007; 46(12):3595-604. DOI: 10.1021/bi700026j. View

20.

Sudhakar A, Ramachandran A, Ghosh S, Hasnain S, Kaufman R, Ramaiah K . Phosphorylation of serine 51 in initiation factor 2 alpha (eIF2 alpha) promotes complex formation between eIF2 alpha(P) and eIF2B and causes inhibition in the guanine nucleotide exchange activity of eIF2B. Biochemistry. 2000; 39(42):12929-38. DOI: 10.1021/bi0008682. View