RRC ID 28896
Author Thomas C, Strutt D.
Title Rabaptin-5 and Rabex-5 are neoplastic tumour suppressor genes that interact to modulate Rab5 dynamics in Drosophila melanogaster.
Journal Dev Biol
Abstract Endocytosis plays an important role in the regulation of tumour growth and metastasis. In Drosophila, a number of endocytic neoplastic tumour suppressor genes have been identified that when mutated cause epithelial disruption and over-proliferation. Here we characterise the Drosophila homologue of the Rab5 effector Rabaptin-5, and show that it is a novel neoplastic tumour suppressor. Its ability to bind Rab5 and modulate early endosomal dynamics is conserved in Drosophila, as is its interaction with the Rab5 GEF Rabex5, for which we also demonstrate neoplastic tumour suppressor characteristics. Surprisingly, we do not observe disruption of apico-basal polarity in Rabaptin-5 and Rabex-5 mutant tissues; instead the tumour phenotype is associated with upregulation of Jun N-terminal Kinase (JNK) and Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signalling.
Volume 385(1)
Pages 107-21
Published 2014-1-1
DOI 10.1016/j.ydbio.2013.09.029
PII S0012-1606(13)00527-7
PMID 24104056
PMC PMC3858806
MeSH Animals Cell Polarity / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Endocytosis / genetics Genes, Tumor Suppressor* JNK Mitogen-Activated Protein Kinases / biosynthesis Janus Kinases / biosynthesis Janus Kinases / metabolism RNA Interference RNA, Small Interfering STAT Transcription Factors / biosynthesis STAT Transcription Factors / metabolism Signal Transduction / genetics Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* Up-Regulation rab5 GTP-Binding Proteins / genetics rab5 GTP-Binding Proteins / metabolism*
IF 2.936
Times Cited 12