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Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruction by the proteasome: Possible etiology for unexplained chronic fatigue

par Englebienne, Patrick;Verhas, Michel ;Herst, Vincent C.V.;De Meirleir, Kenny
Référence Medical hypotheses, 60, 2, page (175-180)
Publication Publié, 2003-02

Article révisé par les pairs

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Résumé :

In some patients complaining of chronic fatigue such as those suffering from the chronic fatigue syndrome (CFS), no underlying physical cause can be clearly identified and they typically present a normal thyroid function. Several studies indicate a dysregulation in the type I interferons (IFN-α/β) pathway in CFS resulting in a sustained upregulation of 2′,5′-oligoadenylate synthetases (2-5OAS). Likewise, patients treated with IFN-α/β usually complain of severe fatigue as a limiting side effect. Beside the 2-5OAS, IFN-α/β induce also the expression of three closely related proteins of unknown function termed the 2-5OAS-like (2-5OASL) proteins. The amino acid sequences of the 2-5OASL proteins display 96% identity with the partial sequence of the thyroid receptor interacting protein (TRIP) 14, further contain two typical thyroid hormone receptor (TR) coregulator domains and feature two ubiquitin C-terminal domains. From these observations, we raise the hypothesis that the 2-5OASL proteins are TRIPs capable of, respectively, repressing TR transactivation and/or signaling the receptor for destruction by the proteasome. Such molecular mechanisms could explain the development of a clinical hypothyroid state in presence of a normal thyroid function. © 2002 Elsevier Science Ltd. All rights reserved.