Intracellular ANKRD1 protein levels are regulated by 26S proteasome-mediated degradation.
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.
Badi
Ileana
I
Dipartimento di Biotecnologie e Scienze Molecolari, Università degli Studi dell'Insubria, Varese, Italy.
Cinquetti
Raffaella
R
Frascoli
Michela
M
Parolini
Cinzia
C
Chiesa
Giulia
G
Taramelli
Roberto
R
Acquati
Francesco
F
D000595:Amino Acid Sequence; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006330:Heart Defects, Congenital / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
C491304:ANKRD1 protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease