Spt5 interacts genetically with Myc and is limiting for brain tumor growth in Drosophila

The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast prolife...

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Published inLife science alliance Vol. 7; no. 1; p. e202302130
Main Authors Hofstetter, Julia, Ogunleye, Ayoola, Kutschke, André, Buchholz, Lisa Marie, Wolf, Elmar, Raabe, Thomas, Gallant, Peter
Format Journal Article
LanguageEnglish
Published United States Life Science Alliance LLC 2024
Subjects
Animals
Brain - metabolism
Brain Neoplasms - genetics
Drosophila - genetics
Drosophila - metabolism
Humans
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Transcriptional Elongation Factors - metabolism
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Abstract The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.
AbstractList The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.
The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use Drosophila to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.
Knockdown of Spt5 in Drosophila affects various Myc-dependent phenotypes and delays the growth of a Myc-dependent brain tumor, thereby significantly extending the longevity of tumorous animals. The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use Drosophila to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.
The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured cells. Here, we use Drosophila to address the relevance of this interaction in a living organism. Spt5 displays moderate synergy with Myc in fast proliferating young imaginal disc cells. During later development, Spt5-knockdown has no detectable consequences on its own, but strongly enhances eye defects caused by Myc overexpression. Similarly, Spt5-knockdown in larval type 2 neuroblasts has only mild effects on brain development and survival of control flies, but dramatically shrinks the volumes of experimentally induced neuroblast tumors and significantly extends the lifespan of tumor-bearing animals. This beneficial effect is still observed when Spt5 is knocked down systemically and after tumor initiation, highlighting SPT5 as a potential drug target in human oncology.
Author Raabe, Thomas
Wolf, Elmar
Buchholz, Lisa Marie
Gallant, Peter
Ogunleye, Ayoola
Kutschke, André
Hofstetter, Julia
AuthorAffiliation 2 https://ror.org/00fbnyb24 Department of Biochemistry and Molecular Biology, Theodor Boveri Institute, Biocenter, University of Würzburg , Würzburg, Germany
1 https://ror.org/00fbnyb24 Cancer Systems Biology Group, Theodor Boveri Institute, Biocenter, University of Würzburg , Würzburg, Germany
3 https://ror.org/00fbnyb24 Molecular Genetics, Biocenter, Am Hubland, University of Würzburg , Würzburg, Germany
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Julia Hofstetter and Ayoola Ogunleye are co-first authors
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Snippet The transcription factor SPT5 physically interacts with MYC oncoproteins and is essential for efficient transcriptional activation of MYC targets in cultured...
Knockdown of Spt5 in Drosophila affects various Myc-dependent phenotypes and delays the growth of a Myc-dependent brain tumor, thereby significantly extending...
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SubjectTerms Animals
Brain - metabolism
Brain Neoplasms - genetics
Drosophila - genetics
Drosophila - metabolism
Humans
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Transcriptional Elongation Factors - metabolism
Title Spt5 interacts genetically with Myc and is limiting for brain tumor growth in Drosophila
URI https://www.ncbi.nlm.nih.gov/pubmed/37935464
https://search.proquest.com/docview/2887476891
https://pubmed.ncbi.nlm.nih.gov/PMC10629571
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