Krüppel-like factor 4 prevents centrosome amplification following γ-irradiation-induced DNA damage

Yoon, Hong Seok; Ghaleb, Amr M.; Nandan, Mandayam O.; Hisamuddin, Irfan M; Dalton, W. Brian; Yang, Vincent W.

doi:10.1038/sj.onc.1208576

Cited by 79 publications

(71 citation statements)

References 53 publications

(72 reference statements)

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“…Expression profiling of KLF4 using cDNA microarray analysis confirmed that KLF4 activates transcription of many additional genes encoding inhibitors of the cell cycle and suppresses those encoding promoters of the cell cycle [20]. Recent studies from our laboratory indicate that KLF4 is also involved in preventing centrosome amplification after γ irradiation [21] and possibly in preventing aneuploidy after spindle damage (Dalton and Yang, unpublished observations). Taken together, these studies point to a wide-ranging and crucial effect of KLF4 in maintaining the integrity of the cell cycle.…”

Section: Klf4 and 5 Exhibit Contrasting Effects On Cellular Proliferamentioning

confidence: 64%

“…KLF4 then exerts a multitude of effects on expression of downstream genes by activating ( ) or inhibiting their expression ( ). References in support of the specific pathways are as follows: p53 KLF4 p21 [16]; KLF4 cyclin D/Cdk4 [19]; KLF4 cyclin B/Cdc2 [18]; KLF4 cyclin E/Cdk2 [21]; KLF4 STK15 [20]; KLF4 14-3-3 σ ; KLF4 BUB1/MAD2 [20].…”

Section: Klf4 and Klf5 Exert Distinct Physiologic Functions In Vivo Amentioning

confidence: 99%

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Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation

et al. 2005

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Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverse regulatory functions in cell growth, proliferation, differentiation, and embryogenesis. KLF4 and KLF5 are two closely related members of the KLF family that have a similar tissue distribution in embryos and adults. However, the two KLFs often exhibit opposite effects on regulation of gene transcription, despite binding to similar, if not identical, cis-acting DNA sequences. In addition, KLF4 and 5 exert contrasting effects on cell proliferation in many instances; while KLF4 is an inhibitor of cell growth, KLF5 stimulates proliferation. Here we review the biological properties and biochemical mechanisms of action of the two KLFs in the context of growth regulation.

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Section: Klf4 and 5 Exhibit Contrasting Effects On Cellular Proliferamentioning

confidence: 64%

Section: Klf4 and Klf5 Exert Distinct Physiologic Functions In Vivo Amentioning

confidence: 99%

Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation

et al. 2005

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“…HCT116 cells contain wild-type (WT) p53 and KLF4 alleles and undergo p21 WAF1/CIP1 -mediated cell cycle arrest following g-irradiation (Yoon et al, 2003;Yoon and Yang, 2004). We previously developed a clonal derivative of HCT116, called HCT116-KLF4/sh2-2, in which expression of KLF4 is significantly reduced owing to the presence of small hairpin RNA (shRNA) against KLF4 (Yoon et al, 2005). Following g-irradiation, HCT116-KLF4/sh2-2 cells exhibited a significantly higher percentage of cells in the sub-G 1 fraction than the control cells, HCT116-KLF4/sh-c ( Figure 3a and Supplementary Figure 2).…”

Section: Apoptosis Of Rko Human Cancer Cells Caused By G-irradiation mentioning

confidence: 99%

“…Control cells were treated with vehicle (ethanol) alone. The HCT116 colon cancer cell lines transfected with shRNA against KLF4 (HCT116-KLF4/ sh2-2) or vector-alone control (HCT116-KLF4/sh-c), were previously established (Yoon et al, 2005). HCT116 cells that are either WT, homozygous null for BAX or homozygous null for p21 WAF1/CIP1 were also used.…”

Section: Cell Linesmentioning

confidence: 99%

Krüppel-like factor 4 exhibits antiapoptotic activity following γ-radiation-induced DNA damage

et al. 2006

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“…In addition to mediating a G1/S block, KLF4 prevents cells to enter mitosis with damaged DNA (Yoon et al, 2005), and indeed it binds to and represses the Cyclin B2 promoter directly (Yoon and Yang, 2004). Finally, and most importantly, in combination with OCT4, SOX2 and Nanog, KLF4 reprograms a wide range of differentiated cells into iPS, a state resembling very closely, if not identical to, totipotent embryonic stem cells (Takahashi and Yamanaka, 2006).…”

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confidence: 99%

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

et al. 2010

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Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.

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Krüppel-like factor 4 prevents centrosome amplification following γ-irradiation-induced DNA damage

Cited by 79 publications

References 53 publications

Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation

Krüppel-like factors 4 and 5: the yin and yang regulators of cellular proliferation

Krüppel-like factor 4 exhibits antiapoptotic activity following γ-radiation-induced DNA damage

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

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