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Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II.
Mol Cell Biol. 2007 Dec; 27(23):8228-42.MC

Abstract

Both transforming growth factor beta (TGF-beta) and p53 have been shown to control normal cell growth. Acquired mutations either in the TGF-beta signaling pathway or in the p53 protein were shown to induce malignant transformation. Recently, cross talk between wild-type p53 and the TGF-beta pathway was observed. The notion that mutant p53 interferes with the wild-type p53-induced pathway and acts by a "gain-of-function" mechanism prompted us to investigate the effect of mutant p53 on the TGF-beta-induced pathway. In this study, we show that cells expressing mutant p53 lost their sensitivity to TGF-beta1, as observed by less cell migration and a reduction in wound healing. We found that mutant p53 attenuates TGF-beta1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus. Furthermore, we found that mutant p53 attenuates the TGF-beta1-induced transcription activity of SMAD2/3 proteins. In searching for the mechanism that underlies this attenuation, we found that mutant p53 reduces the expression of TGF-beta receptor type II. These data provide important insights into the molecular mechanisms that underlie mutant p53 "gain of function" pertaining to the TGF-beta signaling pathway.

Authors+Show Affiliations

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17875924

Citation

Kalo, Eyal, et al. "Mutant P53 Attenuates the SMAD-dependent Transforming Growth Factor Beta1 (TGF-beta1) Signaling Pathway By Repressing the Expression of TGF-beta Receptor Type II." Molecular and Cellular Biology, vol. 27, no. 23, 2007, pp. 8228-42.
Kalo E, Buganim Y, Shapira KE, et al. Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II. Mol Cell Biol. 2007;27(23):8228-42.
Kalo, E., Buganim, Y., Shapira, K. E., Besserglick, H., Goldfinger, N., Weisz, L., Stambolsky, P., Henis, Y. I., & Rotter, V. (2007). Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II. Molecular and Cellular Biology, 27(23), 8228-42.
Kalo E, et al. Mutant P53 Attenuates the SMAD-dependent Transforming Growth Factor Beta1 (TGF-beta1) Signaling Pathway By Repressing the Expression of TGF-beta Receptor Type II. Mol Cell Biol. 2007;27(23):8228-42. PubMed PMID: 17875924.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutant p53 attenuates the SMAD-dependent transforming growth factor beta1 (TGF-beta1) signaling pathway by repressing the expression of TGF-beta receptor type II. AU - Kalo,Eyal, AU - Buganim,Yosef, AU - Shapira,Keren E, AU - Besserglick,Hilla, AU - Goldfinger,Naomi, AU - Weisz,Lilach, AU - Stambolsky,Perry, AU - Henis,Yoav I, AU - Rotter,Varda, Y1 - 2007/09/17/ PY - 2007/9/19/pubmed PY - 2007/12/14/medline PY - 2007/9/19/entrez SP - 8228 EP - 42 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 27 IS - 23 N2 - Both transforming growth factor beta (TGF-beta) and p53 have been shown to control normal cell growth. Acquired mutations either in the TGF-beta signaling pathway or in the p53 protein were shown to induce malignant transformation. Recently, cross talk between wild-type p53 and the TGF-beta pathway was observed. The notion that mutant p53 interferes with the wild-type p53-induced pathway and acts by a "gain-of-function" mechanism prompted us to investigate the effect of mutant p53 on the TGF-beta-induced pathway. In this study, we show that cells expressing mutant p53 lost their sensitivity to TGF-beta1, as observed by less cell migration and a reduction in wound healing. We found that mutant p53 attenuates TGF-beta1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus. Furthermore, we found that mutant p53 attenuates the TGF-beta1-induced transcription activity of SMAD2/3 proteins. In searching for the mechanism that underlies this attenuation, we found that mutant p53 reduces the expression of TGF-beta receptor type II. These data provide important insights into the molecular mechanisms that underlie mutant p53 "gain of function" pertaining to the TGF-beta signaling pathway. SN - 1098-5549 UR - https://www.unboundmedicine.com/medline/citation/17875924/Mutant_p53_attenuates_the_SMAD_dependent_transforming_growth_factor_beta1__TGF_beta1__signaling_pathway_by_repressing_the_expression_of_TGF_beta_receptor_type_II_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=17875924 DB - PRIME DP - Unbound Medicine ER -