Intracellular ANKRD1 protein levels are regulated by 26S proteasome-mediated degradation

Badi, Ileana; Cinquetti, Raffaella; Frascoli, Michela; Parolini, Cinzia; Chiesa, Giulia; Taramelli, Roberto; Acquati, Francesco

doi:10.1016/j.febslet.2009.07.001

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Volume 583, Issue 15 , Pages 2486-2492, 6 August 2009

Intracellular ANKRD1 protein levels are regulated by 26S proteasome-mediated degradation

Edited by Zhijie Chang

Ileana Badi
- Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell’Insubria, Via JH Dunant 3 – 21100 Varese, Italy
- These authors contributed equally to this work.
Raffaella Cinquetti
- Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell’Insubria, Via JH Dunant 3 – 21100 Varese, Italy
- These authors contributed equally to this work.
Michela Frascoli
- Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell’Insubria, Via JH Dunant 3 – 21100 Varese, Italy
Cinzia Parolini
- Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti 9 – 20133 Milan, Italy
Giulia Chiesa
- Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti 9 – 20133 Milan, Italy
Roberto Taramelli
- Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell’Insubria, Via JH Dunant 3 – 21100 Varese, Italy
- Present address: Department of Anatomy and Embryology, Academic Medical Center, Meibergdreef 15 (L2-104), 1105 AZ Amsterdam, The Netherlands.
Francesco Acquati
- Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell’Insubria, Via JH Dunant 3 – 21100 Varese, Italy
- Present address: Department of Anatomy and Embryology, Academic Medical Center, Meibergdreef 15 (L2-104), 1105 AZ Amsterdam, The Netherlands.
- Corresponding author. Fax: +39 0332 421500.

Received 2 December 2008; received in revised form 29 June 2009; accepted 1 July 2009. published online 07 July 2009.

Abstract

The ANKRD1/CARP gene encodes a muscle-specific protein which has been implicated in transcriptional regulation and myofibrillar assembly. Several features at both the mRNA and protein levels define ANKRD1 as a gene whose expression is tightly regulated, and deregulated expression of this protein has been recently associated to human congenital heart disease. It is therefore crucial to define the intracellular pathways that regulate the ANKRD1 protein’s steady-state levels. Here, we show that ANKRD1 is a short-lived protein whose levels are tightly regulated by the 26S proteasome. In addition, a critical role for a putative PEST motif was established, although other degrons within the ANKRD1 protein are likely implicated in the control of its intracellular levels.

Keywords: 26S proteasome, ANKRD1, PEST sequence, Cardiac transcriptional regulator