TY  - JOUR
A1  - Herter, Eva K.
A1  - Stauch, Maria
A1  - Gallant, Maria
A1  - Wolf, Elmar
A1  - Raabe, Thomas
A1  - Gallant, Peter
T1  - snoRNAs are a novel class of biologically relevant Myc targets
JF  - BMC Biology
N2  - Background
Myc proteins are essential regulators of animal growth during normal development, and their deregulation is one of the main driving factors of human malignancies. They function as transcription factors that (in vertebrates) control many growth- and proliferation-associated genes, and in some contexts contribute to global gene regulation.

Results
We combine chromatin immunoprecipitation-sequencing (ChIPseq) and RNAseq approaches in Drosophila tissue culture cells to identify a core set of less than 500 Myc target genes, whose salient function resides in the control of ribosome biogenesis. Among these genes we find the non-coding snoRNA genes as a large novel class of Myc targets. All assayed snoRNAs are affected by Myc, and many of them are subject to direct transcriptional activation by Myc, both in Drosophila and in vertebrates. The loss of snoRNAs impairs growth during normal development, whereas their overexpression increases tumor mass in a model for neuronal tumors.

Conclusions
This work shows that Myc acts as a master regulator of snoRNP biogenesis. In addition, in combination with recent observations of snoRNA involvement in human cancer, it raises the possibility that Myc’s transforming effects are partially mediated by this class of non-coding transcripts.
KW  - Drosophila
KW  - ribosome
KW  - snoRNA
KW  - Myc Transcription
KW  - growth
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124956
VL  - 13
IS  - 25
ER  - 
TY  - JOUR
A1  - Hofstetter, Julia
A1  - Ogunleye, Ayoola
A1  - Kutschke, André
A1  - Buchholz, Lisa Marie
A1  - Wolf, Elmar
A1  - Raabe, Thomas
A1  - Gallant, Peter
T1  - Spt5 interacts genetically with Myc and is limiting for brain tumor growth in Drosophila
JF  - Life Science Alliance
N2  - 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.
KW  - Drosophila
KW  - transcription factor SPT5
KW  - Myc
KW  - brain tumor
KW  - tumor growth
Y1  - 2024
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350197
SN  - 2575-1077
VL  - 7
IS  - 1
ER  -