Diadenosine oligophosphates (Ap n A), a novel class of signalling molecules?

FEBS Letters

Frolova, Lyudmila Yu²  Justesen, Just¹  Wolfson, Alexey D³  Kisselev, Lev L² 

[1] Institute of Molecular and Structural Biology, University of Aarhus, Aarhus, Denmark;U248 INSERM, Institut Curie, Paris, France;Department of Biochemistry, University of Colorado, Boulder, CO, USA

关键词: Diadenosine oligophosphate;    Signal transduction;    Fhit;    2-5A synthetase;    Tryptophanyl-tRNA synthetase;    Tumour suppression;   

DOI  :  10.1016/S0014-5793(98)00420-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The diadenosine oligophosphates (Ap _n A) were discovered in the mid-sixties in the course of studies on aminoacyl-tRNA synthetases (aaRS). Now, more than 30 years later, about 300 papers have been published around these substances in attempt to decipher their role in cells. Recently, Ap _n A have emerged as intracellular and extracellular signalling molecules implicated in the maintenance and regulation of vital cellular functions and become considered as second messengers. Great variety of physiological and pathological effects in mammalian cells was found to be associated with alterations of Ap _n A levels (n from 2 to 6) and Ap₃A/Ap₄A ratio. Cell differentiation and apoptosis have substantial and opposite effects on Ap₃A/Ap₄A ratio in cultured cells. A human Ap₃A hydrolase, Fhit, appeared to be involved in protection of cells against tumourigenesis. Ap₃A is synthesised by mammalian u synthetase (TrpRS) which in contrast to most other aaRS is unable to synthesise Ap₄A and is an interferon-inducible protein. Moreover, Ap₃A appeared to be a preferred substrate for 2-5A synthetase, also interferon-inducible, priming the synthesis of 2′ adenylated derivatives of Ap₃A, which in turn may serve as substrates of Fhit. Tumour suppressor activity of Fhit is assumed to be associated with involvement of the Fhit·Ap₃A complex in cytokine signalling pathway(s) controlling cell proliferation. The Ap _n A family is potentially a novel class of signal-transducing molecules whose functions are yet to be determined.

【 授权许可】

Unknown