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Abstract 3086: Interactions of nucleolin and ribosomal protein RPL26 in the translational control of human p53 mRNA

Publication ,  Journal Article
Chen, J; Guo, K; Kastan, MB
Published in: Cancer Research
April 15, 2011

Our lab has previously shown that the ribosomal protein RPL26 enhances p53 translation and induction after DNA damage and that this regulation depends upon interactions between the 5′ and 3′ untranslated regions (UTR) of human p53 mRNA (Takagi et al Cell, 2005; Chen & Kastan, Genes & Dev, 2010). In contrast, nucleolin (NCL), a multifunctional nucleolar protein, suppresses the translation of human p53 mRNA and its induction after DNA damage. Interestingly, RPL26 and NCL also interact with each other. In order to understand how these two proteins cooperate with/antagonize each other to regulate p53 translation after stress, we first recapitulated the translational control of p53 by NCL in both an in vitro transcription/translation system and a cell-based, luciferase reporter system. In both systems, NCL repression required the presence of both the 5′UTR and 3′UTR of p53 mRNA. Further, NCL binds to the same 5′-3′ UTR interaction region that is critical for RPL26 recruitment after DNA damage. We also observed that NCL protein interacts with itself; the ability of NCL to dimerize/oligomerize and its reported ability to stabilize double strand nucleic acid structures suggests the possibility that NCL may stabilize the double-strand RNA structure involving the two p53 mRNA UTR's. Domain mapping demonstrated that the RNA binding domain of NCL participates in binding to p53 mRNA, is required for both NCL dimerization and NCL-mediated translational repression, and is the domain of NCL that interacts with RPL26. RPL26 was able to disrupt NCL dimerization in cell-based immunoprecipitation assays. We also identified the domain of RPL26 that is required to interact with nucleolin and found that point mutations in this region of RPL26 reduce RPL26-NCL interactions and attenuate both RPL26 binding to human p53 mRNA and p53 induction by RPL26. These observations taken together suggest a model for the interplay of NCL and RPL26 in the translational control of human p53 mRNA after DNA damage: NCL binds both p53 UTR's and NCL dimerization/oligomerization facilitates the double strand RNA structure by stabilizing the base pairing between the 5′ and 3′ UTR's. This “closed” structure of p53 mRNA might inhibit its translation by affecting the access of general translational machinery to the message. Upon stress stimulation, RPL26 binds to this double-stranded RNA structure containing the two UTR's and occupied by NCL, leading to a disruption of NCL dimerization and enhancement of p53 translation.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3086. doi:10.1158/1538-7445.AM2011-3086

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2011

Volume

71

Issue

8_Supplement

Start / End Page

3086 / 3086

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, J., Guo, K., & Kastan, M. B. (2011). Abstract 3086: Interactions of nucleolin and ribosomal protein RPL26 in the translational control of human p53 mRNA. Cancer Research, 71(8_Supplement), 3086–3086. https://doi.org/10.1158/1538-7445.am2011-3086
Chen, Jing, Kexiao Guo, and Michael B. Kastan. “Abstract 3086: Interactions of nucleolin and ribosomal protein RPL26 in the translational control of human p53 mRNA.” Cancer Research 71, no. 8_Supplement (April 15, 2011): 3086–3086. https://doi.org/10.1158/1538-7445.am2011-3086.
Chen J, Guo K, Kastan MB. Abstract 3086: Interactions of nucleolin and ribosomal protein RPL26 in the translational control of human p53 mRNA. Cancer Research. 2011 Apr 15;71(8_Supplement):3086–3086.
Chen, Jing, et al. “Abstract 3086: Interactions of nucleolin and ribosomal protein RPL26 in the translational control of human p53 mRNA.” Cancer Research, vol. 71, no. 8_Supplement, American Association for Cancer Research (AACR), Apr. 2011, pp. 3086–3086. Crossref, doi:10.1158/1538-7445.am2011-3086.
Chen J, Guo K, Kastan MB. Abstract 3086: Interactions of nucleolin and ribosomal protein RPL26 in the translational control of human p53 mRNA. Cancer Research. American Association for Cancer Research (AACR); 2011 Apr 15;71(8_Supplement):3086–3086.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2011

Volume

71

Issue

8_Supplement

Start / End Page

3086 / 3086

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis