Up-regulation of SEPT9_v1 stabilizes c-Jun-N-Terminal kinase and contributes to its pro-proliferative activity in mammary epithelial cells

Maria E. Gonzalez, Olga Makarova, Esther A. Peterson, Lisa M. Privette, Elizabeth M. Petty

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

SEPT9_v1, the largest transcript of the septin gene family member, SEPT9, encodes a septin isoform implicated in the tumorigenic transformation of mammary epithelial cells. High levels of SEPT9_v1 expression also have been observed in both breast cancer cell lines, primary breast cancers as well as other solid tumor malignancies. We found a novel interaction between SEPT9_v1 and the c-Jun-N-terminal kinase (JNK), a mitogen-activated protein kinase important in cellular stress responses, cell proliferation, and cell survival. We found that up-regulation of SEPT9_v1 stabilizes JNK by delaying its degradation, thereby activating the JNK transcriptome. C-jun kinase assays in mammary epithelial cells expressing SEPT9_v1, compared to controls, exhibited increased JNK/c-Jun transcriptional activity. This increase was associated with increased levels of cyclin D1, a critical component of the proliferative response required for progression through G 1 of the cell cycle in many cell types. These findings demonstrate the first link between a septin protein and the JNK signaling pathway. Importantly, it suggests a novel functional role of SEPT9_v1 in driving cellular proliferation of mammary epithelial cells, a hallmark feature of oncogenesis that is directly relevant to breast cancer.

Original languageEnglish (US)
Pages (from-to)477-487
Number of pages11
JournalCellular Signalling
Volume21
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Fingerprint

JNK Mitogen-Activated Protein Kinases
Septins
Breast
Phosphotransferases
Up-Regulation
Epithelial Cells
Breast Neoplasms
Neoplastic Cell Transformation
Cell Proliferation
Gastrin-Secreting Cells
Cyclin D1
Mitogen-Activated Protein Kinases
Transcriptome
Neoplasms
Cell Survival
Cell Cycle
Protein Isoforms
Carcinogenesis
Cell Line
Genes

Keywords

  • Cell cycle regulation
  • Cell proliferation
  • Cyclins
  • JNK
  • Mammary epithelial cells
  • Oncogenesis
  • Septins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Up-regulation of SEPT9_v1 stabilizes c-Jun-N-Terminal kinase and contributes to its pro-proliferative activity in mammary epithelial cells. / Gonzalez, Maria E.; Makarova, Olga; Peterson, Esther A.; Privette, Lisa M.; Petty, Elizabeth M.

In: Cellular Signalling, Vol. 21, No. 4, 04.2009, p. 477-487.

Research output: Contribution to journalArticle

Gonzalez, Maria E. ; Makarova, Olga ; Peterson, Esther A. ; Privette, Lisa M. ; Petty, Elizabeth M. / Up-regulation of SEPT9_v1 stabilizes c-Jun-N-Terminal kinase and contributes to its pro-proliferative activity in mammary epithelial cells. In: Cellular Signalling. 2009 ; Vol. 21, No. 4. pp. 477-487.
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