Ubiquilin-1 is a novel HASH-1-complexing protein that regulates levels of neuronal bHLH transcription factors in human neuroblastoma cells.
The basic helix-loop-helix (bHLH) transcription factor mammalian achaete-scute homologue-1 (MASH-1 in mouse and HASH-1 in humans) is expressed in specific subsets of embryonic neuronal precursors of both the peripheral and central nervous systems. This gene is essential for development of olfactory and most peripheral autonomic neurons. Neuro-blastoma is a pediatric malignancy derived from sympathetic nervous system precursors and HASH-1 is expressed in a majority of neuroblastoma tumors and cell lines, indicating the immature phenotype of these cells. Using a human neuroblastoma cDNA library and the yeast two-hybrid system to identify novel HASH-1-interacting proteins, we isolated ubiquilin-1 (DA41, hPLIC-1), a gene that contains multiple ubiquitin-related domains. Further analyses showed that ubiquilin-1 interacts not only with HASH-1, but also with other tissue-specific bHLH proteins, including HES-1. Overexpression of ubiquilin-1 led to accumulation of HASH-1 and HES-1. Moreover, ubiquilin-1 was translocated from the cytoplasm to the nucleus upon co-expression with HASH-1. These results indicate that ubiquilin-1 plays an active role in the precise regulation of HASH-1 and of other tissue-specific bHLH proteins.
Persson
Paula
P
Department of Laboratory Medicine, Division of Molecular Medicine, Lund University, University Hospital MAS, S-205 02 Malmö, Sweden.
Stockhausen
Marie-Thérése
MT
Påhlman
Sven
S
Axelson
Håkan
H
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D004815:Epidermal Growth Factor; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D009687:Nuclear Proteins; D016716:PC12 Cells; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015003:Yeasts / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor; D009687:Nuclear Proteins; D014157:Transcription Factors; C065500:ASCL1 protein, human; C499318:Ascl1 protein, rat; C107792:UBQLN1 protein, human