Abstract/Details

Acheron, a novel regulator of myoblast differentiation


2003 2003

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Abstract (summary)

Programmed cell death is essential for normal development and adult tissue homeostasis in almost all multicelluar organisms. Acheron gene was first isolated from the intersegmental muscles (ISMs) in Manduca sexta as a death-associated gene. Subsequently, we cloned human and mouse homolog of Acheron. Acheron encodes a novel protein that has not been previously characterized. Protein structure analysis revealed that Acheron proteins are structurally related to La proteins, but define a novel subfamily. Tissue expression analysis showed that mAcheron is widely expressed in most tissues at both the RNA and protein levels, with brain and heart displaying the highest levels.

In mouse C2C12 cells, endogenous Acheron is constitutively expressed in cycling myoblasts and myotubes. Despite the presence of a putative nuclear localization site, the protein is localized predominantly in the cytoplasm. Analyses of the different Acheron transfected C2C12 cells suggested that Acheron is implicated in mediating differentiation and apoptosis in C2C12 cells by differentially regulating the expression of MyoD, Myf5 and Bcl-2. Acheron expression allows C2 C12 cells to up-regulate MyoD and differentiate into myotubes when the cells are induced to undergo differentiation. However, it does not support the myoblast self-renewal by specifically inhibiting the expression of Bcl-2, a key survival factor for ‘reserve’ cells in DM. Inhibition of Acheron activity by tAch (a putative dominant negative regulatory factor of Acheron) or antisense Acheron results in greatly increased ‘reserve’ cell population and decreased differentiation under differentiation condition. The mediation of differentiation and survival by Acheron may be achieved through its regulation on integrin—FAK signaling.

To help determine how Acheron functions, we performed a yeast 2-hybrid screen with Acheron as the bait. A clone that contains partial cDNA of Ariadne was isolated from the screen. Ariadne contains RING finger domain and is known to bind to ubiquitin E2 conjugase. In vitro ubiquitination assay revealed that Ariadne has ubiquitin E3 ligase activity. We speculate that Ariadne may function as an E3 to target Acheron for ubiquitination and subsequent proteasome-dependent degradation.

Indexing (details)


Subject
Cellular biology;
Molecular biology
Classification
0379: Cellular biology
0307: Molecular biology
Identifier / keyword
Biological sciences; Acheron; Differentiation; Myoblast
Title
Acheron, a novel regulator of myoblast differentiation
Author
Wang, Zhaohui
Number of pages
172
Publication year
2003
Degree date
2003
School code
0118
Source
DAI-B 64/01, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
0493997520, 9780493997520
Advisor
Schwartz, Lawrence M.
University/institution
University of Massachusetts Amherst
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3078726
ProQuest document ID
305321879
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305321879
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