Krüppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation

Mandayam O. Nandan, Sengthong Chanchevalap, William Dalton, Vincent W. Yang

Research output: Contribution to journalArticle

Abstract

We previously showed that the zinc finger-containing transcription factor Krüppel-like factor 5 (KLF5) is important in mediating transformation by oncogenic H-Ras through induction of cyclin D1 expression and acceleration of the G1/S transition of the cell cycle. Here we present evidence of a role for KLF5 in accelerating mitotic entry in H-Ras-transformed NIH3T3 fibroblasts. When compared with non-transformed parental NIH3T3 cells, H-Ras-transformed fibroblasts exhibit an increase in mitotic index, levels of cyclin B1 and Cdc2, and cyclin B1/Cdc2 kinase activity. Inhibition of KLF5 expression in H-Ras-transformed cells with KLF5-specific small interfering RNA (siRNA) results in a decrease in each of the aforementioned parameters, with a concomitant reduction in the transforming potential of the cells. Conversely, over-expression of KLF5 in NIH3T3 cells leads to an increase in the promoter activity of the genes encoding cyclin B1 and Cdc2. These results indicate that KLF5 accelerates mitotic entry in H-Ras-transformed cells by transcriptionally activating cyclin B1 and Cdc2, which leads to an increase in cyclin B1/Cdc2 kinase activity. Extending our previous observation that KLF5 activates cyclin D1 transcription to promote G1/S transition, our current results further support a crucial function for KLF5 in mediating cellular transformation caused by oncogenic H-Ras.

Original languageEnglish (US)
Pages (from-to)4757-4762
Number of pages6
JournalFEBS Letters
Volume579
Issue number21
DOIs
StatePublished - Aug 29 2005
Externally publishedYes

Fingerprint

Cyclin B1
Mitosis
Cyclin D1
Fibroblasts
Phosphotransferases
Mitotic Index
Gene encoding
Zinc Fingers
Transcription
Small Interfering RNA
Zinc
Cell Cycle
Transcription Factors
Cells
Genes

Keywords

  • Colony formation
  • G/M transition
  • Mitotic index
  • Proliferation
  • Small interfering RNA
  • Transformation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Krüppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation. / Nandan, Mandayam O.; Chanchevalap, Sengthong; Dalton, William; Yang, Vincent W.

In: FEBS Letters, Vol. 579, No. 21, 29.08.2005, p. 4757-4762.

Research output: Contribution to journalArticle

Nandan, Mandayam O. ; Chanchevalap, Sengthong ; Dalton, William ; Yang, Vincent W. / Krüppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation. In: FEBS Letters. 2005 ; Vol. 579, No. 21. pp. 4757-4762.
@article{d91b7563582e41029bbcfb9863c2b7df,
title = "Kr{\"u}ppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation",
abstract = "We previously showed that the zinc finger-containing transcription factor Kr{\"u}ppel-like factor 5 (KLF5) is important in mediating transformation by oncogenic H-Ras through induction of cyclin D1 expression and acceleration of the G1/S transition of the cell cycle. Here we present evidence of a role for KLF5 in accelerating mitotic entry in H-Ras-transformed NIH3T3 fibroblasts. When compared with non-transformed parental NIH3T3 cells, H-Ras-transformed fibroblasts exhibit an increase in mitotic index, levels of cyclin B1 and Cdc2, and cyclin B1/Cdc2 kinase activity. Inhibition of KLF5 expression in H-Ras-transformed cells with KLF5-specific small interfering RNA (siRNA) results in a decrease in each of the aforementioned parameters, with a concomitant reduction in the transforming potential of the cells. Conversely, over-expression of KLF5 in NIH3T3 cells leads to an increase in the promoter activity of the genes encoding cyclin B1 and Cdc2. These results indicate that KLF5 accelerates mitotic entry in H-Ras-transformed cells by transcriptionally activating cyclin B1 and Cdc2, which leads to an increase in cyclin B1/Cdc2 kinase activity. Extending our previous observation that KLF5 activates cyclin D1 transcription to promote G1/S transition, our current results further support a crucial function for KLF5 in mediating cellular transformation caused by oncogenic H-Ras.",
keywords = "Colony formation, G/M transition, Mitotic index, Proliferation, Small interfering RNA, Transformation",
author = "Nandan, {Mandayam O.} and Sengthong Chanchevalap and William Dalton and Yang, {Vincent W.}",
year = "2005",
month = "8",
day = "29",
doi = "10.1016/j.febslet.2005.07.053",
language = "English (US)",
volume = "579",
pages = "4757--4762",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "21",

}

TY - JOUR

T1 - Krüppel-like factor 5 promotes mitosis by activating the cyclin B1/Cdc2 complex during oncogenic Ras-mediated transformation

AU - Nandan, Mandayam O.

AU - Chanchevalap, Sengthong

AU - Dalton, William

AU - Yang, Vincent W.

PY - 2005/8/29

Y1 - 2005/8/29

N2 - We previously showed that the zinc finger-containing transcription factor Krüppel-like factor 5 (KLF5) is important in mediating transformation by oncogenic H-Ras through induction of cyclin D1 expression and acceleration of the G1/S transition of the cell cycle. Here we present evidence of a role for KLF5 in accelerating mitotic entry in H-Ras-transformed NIH3T3 fibroblasts. When compared with non-transformed parental NIH3T3 cells, H-Ras-transformed fibroblasts exhibit an increase in mitotic index, levels of cyclin B1 and Cdc2, and cyclin B1/Cdc2 kinase activity. Inhibition of KLF5 expression in H-Ras-transformed cells with KLF5-specific small interfering RNA (siRNA) results in a decrease in each of the aforementioned parameters, with a concomitant reduction in the transforming potential of the cells. Conversely, over-expression of KLF5 in NIH3T3 cells leads to an increase in the promoter activity of the genes encoding cyclin B1 and Cdc2. These results indicate that KLF5 accelerates mitotic entry in H-Ras-transformed cells by transcriptionally activating cyclin B1 and Cdc2, which leads to an increase in cyclin B1/Cdc2 kinase activity. Extending our previous observation that KLF5 activates cyclin D1 transcription to promote G1/S transition, our current results further support a crucial function for KLF5 in mediating cellular transformation caused by oncogenic H-Ras.

AB - We previously showed that the zinc finger-containing transcription factor Krüppel-like factor 5 (KLF5) is important in mediating transformation by oncogenic H-Ras through induction of cyclin D1 expression and acceleration of the G1/S transition of the cell cycle. Here we present evidence of a role for KLF5 in accelerating mitotic entry in H-Ras-transformed NIH3T3 fibroblasts. When compared with non-transformed parental NIH3T3 cells, H-Ras-transformed fibroblasts exhibit an increase in mitotic index, levels of cyclin B1 and Cdc2, and cyclin B1/Cdc2 kinase activity. Inhibition of KLF5 expression in H-Ras-transformed cells with KLF5-specific small interfering RNA (siRNA) results in a decrease in each of the aforementioned parameters, with a concomitant reduction in the transforming potential of the cells. Conversely, over-expression of KLF5 in NIH3T3 cells leads to an increase in the promoter activity of the genes encoding cyclin B1 and Cdc2. These results indicate that KLF5 accelerates mitotic entry in H-Ras-transformed cells by transcriptionally activating cyclin B1 and Cdc2, which leads to an increase in cyclin B1/Cdc2 kinase activity. Extending our previous observation that KLF5 activates cyclin D1 transcription to promote G1/S transition, our current results further support a crucial function for KLF5 in mediating cellular transformation caused by oncogenic H-Ras.

KW - Colony formation

KW - G/M transition

KW - Mitotic index

KW - Proliferation

KW - Small interfering RNA

KW - Transformation

UR - http://www.scopus.com/inward/record.url?scp=24044512379&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24044512379&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2005.07.053

DO - 10.1016/j.febslet.2005.07.053

M3 - Article

C2 - 16102754

AN - SCOPUS:24044512379

VL - 579

SP - 4757

EP - 4762

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 21

ER -