TRRAP is essential for regulating the accumulation of mutant and wild-type p53 in lymphoma

Author:

Jethwa Alexander12ORCID,Słabicki Mikołaj1ORCID,Hüllein Jennifer12,Jentzsch Marius1,Dalal Vineet12,Rabe Sophie23ORCID,Wagner Lena1,Walther Tatjana1,Klapper Wolfram4ORCID,Bohnenberger Hanibal5ORCID,Rettel Mandy6ORCID,Lu Junyan6ORCID,Smits Arne H.6ORCID,Stein Frank6ORCID,Savitski Mikhail M.6ORCID,Huber Wolfgang6ORCID,Aylon Yael7,Oren Moshe7ORCID,Zenz Thorsten138ORCID,

Affiliation:

1. Molecular Therapy in Haematology and Oncology, Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center (DKFZ), Heidelberg, Germany;

2. Faculty of Biosciences, Heidelberg University, Heidelberg, Germany;

3. Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany;

4. Hematopathology Section and Lymph Node Registry, Department of Pathology, University Hospital Schleswig-Holstein, Campus Kiel, Christian Albrechts University Kiel, Kiel, Germany;

5. Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany;

6. European Molecular Biology Laboratory, Heidelberg, Germany;

7. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; and

8. Department of Hematology, University Hospital and University of Zürich, Zürich, Switzerland

Abstract

Key Points The HAT complex member TRRAP is vital for maintaining high p53 levels by shielding it against the natural p53 degradation machinery. Acetylation-modifying complexes regulate p53 protein stability, which may provide a basis for therapeutic targeting of mutant p53.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference72 articles.

1. Burkitt’s lymphoma;Molyneux;Lancet,2012

2. The pattern of p53 mutations in Burkitt’s lymphoma differs from that of solid tumors;Bhatia;Cancer Res,1992

3. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia;Gaidano;Proc Natl Acad Sci USA,1991

4. Mutant p53 gain-of-function in cancer;Oren;Cold Spring Harb Perspect Biol,2010

5. When mutants gain new powers: news from the mutant p53 field;Brosh;Nat Rev Cancer,2009

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