Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331- induced apoptosis

Tze Sing Huang, Chih Hung Shu, Wen K. Yang, Jacqueline Whang-Peng

Research output: Contribution to journalArticle

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Abstract

CDC 25 is a dual phosphatase responsible for dephosphorylation and, thus, activation of CDC 2 kinase in G2. Abnormal activation of cyclin B- associated CDC 2 kinase has been implicated in apoptosis induced by cancer chemotherapeutic agents such as paclitaxel (Taxol) and etoposide (VP-16). In this study, we found that the CDC 2 kinase could be transiently activated when nasopharyngeal carcinoma NPC-TW01 cells were treated for 3 h with a new anticancer agent, GL331, GL331 treatment also induced a concomitant increase in CDC 25A phosphatase activity and a reduced level of Tyr-15-phosphorylated CDC 2 in NPC-TW01 cells. Furthermore, subsequent apoptotic DNA fragmentation induced by GL331 could be interrupted by treatment of the cells with the cyclin B1-specific antisense oligonucleotides, suggesting that abnormal activation of cyclin B1-associated CDC 2 kinase and CDC 25A phosphatase was involved in GL331-induced apoptosis. Raf-1 has been shown to associate with CDC 25A and, thus, to stimulate its phosphatase activity. Our results revealed that GL331 could facilitate the association of CDC 25A with Raf-1, resulting in the cascade of CDC 25A phosphatase activation and CDC 2 kinase activation, as well as related signaling pathways, and ultimately causing apoptosis in cancer cells.

Original languageEnglish
Pages (from-to)2974-2978
Number of pages5
JournalCancer Research
Volume57
Issue number14
Publication statusPublished - Jul 15 1997
Externally publishedYes

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Centers for Disease Control and Prevention (U.S.)
Phosphoric Monoester Hydrolases
Phosphotransferases
Apoptosis
Cyclin B1
Etoposide
Paclitaxel
GL 331
Cyclin B
Antisense Oligonucleotides
DNA Fragmentation
Antineoplastic Agents
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331- induced apoptosis. / Huang, Tze Sing; Shu, Chih Hung; Yang, Wen K.; Whang-Peng, Jacqueline.

In: Cancer Research, Vol. 57, No. 14, 15.07.1997, p. 2974-2978.

Research output: Contribution to journalArticle

Huang, Tze Sing ; Shu, Chih Hung ; Yang, Wen K. ; Whang-Peng, Jacqueline. / Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331- induced apoptosis. In: Cancer Research. 1997 ; Vol. 57, No. 14. pp. 2974-2978.
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