Human Mucin 1 Oncoprotein Represses Transcription of the <i>p53</i> Tumor Suppressor Gene

Wei, Xiaolong; Xu, Haiyan; Küfe, Donald

doi:10.1158/0008-5472.can-06-3063

Cited by 91 publications

(80 citation statements)

References 38 publications

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“…It was also shown that KLF4 suppresses p53 expression by directly acting on its promoter, thus providing resistance to DNA damage-induced apoptosis (Wei et al, 2007). Depleting KLF4 from breast cancer cells restores p53 levels and causes p53-dependent apoptosis (Rowland et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα

et al. 2009

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Kruppel-like factor 4 (KLF4) is a transcription factor that participates in both tumor suppression and oncogenesis. To determine the association of KLF4 with tumorigenesis, we integrated data assembled in the Oncomine database and discovered a decrease in KLF4 gene transcripts in breast cancers. Further analysis of the database also showed a correlation between KLF4 expression and estrogen receptor-a (ERa) positivity. Knockdown of KLF4 in MCF-7 cells elevated the growth rate of these cells in the presence of estrogen. Therefore, we examined the interaction between KLF4 and ERa, and found that KLF4 bound to the DNA-binding region of ERa. KLF4 thus inhibits the binding of ERa to estrogen response elements in promoter regions, resulting in a reduction in ERa target gene transcription. Earlier studies have reported that KLF4 is transcriptionally activated by p53 following DNA damage. We also showed that activation of p53 decreased the transcriptional activity of ERa by elevating KLF4 expression. Our studies discovered a novel molecular network between p53, KLF4 and ERa. As both p53 and ERa are involved in cell growth and apoptosis, these results may explain why KLF4 possesses both tumor suppressive and oncogenic functions in breast cancers.

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Section: Introductionmentioning

confidence: 99%

KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα

et al. 2009

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“…A plethora of partner proteins have been implicated in modulating the selection of p53 targets. The cellular environment and the relative abundance of these partners under different conditions could obviously tip the life-or-death balance of p53 activity (4,(10)(11)(12)(13)(14)(15). Recently, the zinc finger protein Hzf was found to be involved in opposite arms of the p53 response, providing an important insight into the mechanisms that dictate the life and death decisions of p53 (16).…”

Section: Introductionmentioning

confidence: 99%

Role for Krüppel-Like Factor 4 in Determining the Outcome of p53 Response to DNA Damage

Zhou

Yuan²,

Zhan³

et al. 2009

Cancer Research

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Cells are incessantly exposed to many sources of genotoxic stress. A critical unresolved issue is how the resulting activation of the p53 tumor suppressor can lead to either cell cycle arrest or apoptosis depending on the extent of DNA damage. The present study shows that the level of Krüppel-like factor 4 (KLF4) expression is inversely correlated with the extent of DNA damage. KLF4 is activated by p53 following cytostatic, mild DNA damage, whereas it is strongly repressed via enhanced turnover of mRNA on severe DNA damage that irreversibly drives cells to apoptosis. Blocking the repression of KLF4 on severe DNA damage suppresses p53-mediated apoptosis, whereas ablation of the KLF4 induction on mild DNA damage shifts the p53 response from cell cycle arrest to cell death. Our results suggest that coordinate regulation of KLF4 expression depending on the extent of DNA damage may be an important mechanism that dictates the life and death decisions of p53. [Cancer Res 2009;69(21):8284-92]

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“…The cytoplasmic domain (Muc1-c) is targeted toward the nucleus, where it interacts with P53 gene and occupies its promoter region. This makes the kruppel-like factor tightly bound with the promoter region, resulting in suppression of gene P53 [18] [19]. When gene P53 becomes inactive, this leads to suppression of P21 (cyclin dependent-kinase inhibitor) which results in prevention of cyclic arrest.…”

Section: Blocking the Pathway Of The Intrinsic Program Of Cell Deathmentioning

confidence: 99%

Quranic Verse No. 8 of Surat Al-Jumu’ah Describes Cancer as a Complete and Accurate Description and Leads Us to Determine the True Cause of Cancer. “Part-1”

El-Khodary¹

2018

CellBio

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Human Mucin 1 Oncoprotein Represses Transcription of the p53 Tumor Suppressor Gene

Cited by 91 publications

References 38 publications

KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα

KLF4 suppresses estrogen-dependent breast cancer growth by inhibiting the transcriptional activity of ERα

Role for Krüppel-Like Factor 4 in Determining the Outcome of p53 Response to DNA Damage

Quranic Verse No. 8 of Surat Al-Jumu’ah Describes Cancer as a Complete and Accurate Description and Leads Us to Determine the True Cause of Cancer. “Part-1”

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