The HBP1 transcriptional repressor participates in RAS-induced premature senescence

Xiaowei Zhang, Jiyoung Kim, Robin Ruthazer, Michael A. McDevitt, David E. Wazer, K. Eric Paulson, Amy S. Yee

Research output: Contribution to journalArticle

Abstract

Oncogene-mediated premature senescence has emerged as a potential tumor-suppressive mechanism in early cancer transitions. Previous work shows that RAS and p38 MAPK participate in premature senescence, but transcriptional effectors have not been identified. Here, we demonstrate that the HBP1 transcriptional repressor participates in RAS- and p38 MAPK-induced premature senescence. In cell lines, we had previously isolated HBP1 as a retinoblastoma (RB) target but have determined that it functions as a proliferation regulator by inhibiting oncogenic pathways as a transcriptional repressor. In primary cells, the results indicate that HBP1 is a necessary component of premature senescence by RAS and p38 MAPK. Similarly, a knockdown of WIP1 (a p38 MAPK phosphatase) induced premature senescence that also required HBP1. Furthermore, HBP1 requires regulation by RB, in which few transcriptional regulators for premature senescence have been shown. Together, the data suggest a model in which RAS and p38 MAPK signaling engage HBP1 and RB to trigger premature senescence. As an initial step toward clinical relevance, a bioinformatics approach shows that the relative expression levels of HBP1 and WIP1 correlated with decreased relapse-free survival in breast cancer patients. Together, these studies highlight p38 MAPK, HBP1, and RB as important components for a premature-senescence pathway with possible clinical relevance to breast cancer.

Original languageEnglish (US)
Pages (from-to)8252-8266
Number of pages15
JournalMolecular and Cellular Biology
Volume26
Issue number22
DOIs
StatePublished - Nov 2006

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p38 Mitogen-Activated Protein Kinases
Retinoblastoma
Dual Specificity Phosphatase 1
Breast Neoplasms
Computational Biology
Oncogenes
Neoplasms
Recurrence
Cell Line
Survival

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Zhang, X., Kim, J., Ruthazer, R., McDevitt, M. A., Wazer, D. E., Paulson, K. E., & Yee, A. S. (2006). The HBP1 transcriptional repressor participates in RAS-induced premature senescence. Molecular and Cellular Biology, 26(22), 8252-8266. https://doi.org/10.1128/MCB.00604-06

The HBP1 transcriptional repressor participates in RAS-induced premature senescence. / Zhang, Xiaowei; Kim, Jiyoung; Ruthazer, Robin; McDevitt, Michael A.; Wazer, David E.; Paulson, K. Eric; Yee, Amy S.

In: Molecular and Cellular Biology, Vol. 26, No. 22, 11.2006, p. 8252-8266.

Research output: Contribution to journalArticle

Zhang, X, Kim, J, Ruthazer, R, McDevitt, MA, Wazer, DE, Paulson, KE & Yee, AS 2006, 'The HBP1 transcriptional repressor participates in RAS-induced premature senescence', Molecular and Cellular Biology, vol. 26, no. 22, pp. 8252-8266. https://doi.org/10.1128/MCB.00604-06
Zhang X, Kim J, Ruthazer R, McDevitt MA, Wazer DE, Paulson KE et al. The HBP1 transcriptional repressor participates in RAS-induced premature senescence. Molecular and Cellular Biology. 2006 Nov;26(22):8252-8266. https://doi.org/10.1128/MCB.00604-06
Zhang, Xiaowei ; Kim, Jiyoung ; Ruthazer, Robin ; McDevitt, Michael A. ; Wazer, David E. ; Paulson, K. Eric ; Yee, Amy S. / The HBP1 transcriptional repressor participates in RAS-induced premature senescence. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 22. pp. 8252-8266.
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