Journal Article

DKFZ-2022-00462

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Rbbp4 loss disrupts neural progenitor cell cycle regulation independent of Rb and leads to Tp53 acetylation and apoptosis.

Schultz-Rogers, L. E. ; Thayer, M. L. ; Kambakam, S. ; Wierson, W. A. ; Helmer, J. A. ; Wishman, M. D. ; Wall, K. A. ; Greig, J. L. ; Forsman, J. L. ; Puchhalapalli, K. ; Nair, S. ; Weiss, T. J. ; Luiken, J. M. ; Blackburn, P. R. ; Ekker, S. C. ; Kool, M.DKFZ* ; McGrail, M.

2022
Wiley New York, NY [u.a.]

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Please use a persistent id in citations: doi:10.1002/dvdy.467

Abstract: Retinoblastoma-binding protein 4 (Rbbp4) is a component of transcription regulatory complexes that control cell cycle gene expression. Previous work indicated Rbbp4 cooperates with the Rb tumor suppressor to block cell cycle entry. Here, we use genetic analysis to examine the interactions of Rbbp4, Rb and Tp53 in zebrafish neural progenitor cell cycle regulation and survival.Rbbp4 is upregulated across the spectrum of human embryonal and glial brain cancers. Transgenic rescue of rbbp4 mutant embryos shows Rbbp4 is essential for zebrafish neurogenesis. Rbbp4 loss leads to apoptosis and γ-H2AX in the developing brain that is suppressed by tp53 knockdown or maternal zygotic deletion. Mutant retinal neural precursors accumulate in M phase and fail to initiate G0 gene expression. rbbp4; rb1 mutants show an additive effect on the number of M phase cells. In rbbp4 mutants Tp53 acetylation is detected, however, Rbbp4 overexpression did not rescue DNA damage induced apoptosis.Rbbp4 is necessary for neural progenitor cell cycle progression and initiation of G0 independent of Rb. Tp53-dependent apoptosis in the absence of Rbpb4 correlates with Tp53 acetylation. Together these results suggest Rbbp4 is required for cell cycle exit and contributes to neural progenitor survival through regulation of Tp53 acetylation. This article is protected by copyright. All rights reserved.

Note: 2022 Aug;251(8):1267-1290

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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