The enigmatic role of the ankyrin repeat domain 1 gene in heart development and disease

Abstract

It has been proposed that the ankyrin repeat domain 1 (ANKRD1) factor (also known as CARP) plays a critical role in transcriptional regulation, myofibrillar assembly and stretch sensing during heart development and cardiac insults. ANKRD1/CARP has also been reported to negatively regulate cardiac gene expression in cell-based promoter-reporter assays. Consequently, rapid up-regulation of the ankrd1 gene in myocardium in response to developmental stimuli or pathological insults has tended to be interpreted in the context of the inhibitory effects of ANKRD1 on cardiomyocyte gene expression. Surprisingly, a total ankrd1 knockout resulted in a complete lack of phenotype, suggesting that ANKRD1/CARP is not crucial for regulation of cardiac gene expression in vivo. In this essay, we summarize (1) the accumulated evidence for the apparent multifunctional properties of this enigmatic protein, (2) the distinct chamber-dependent regulation of ankrd1 expression patterns in the heart, both during development and cardiac injury, and (3) ANKRD1 involvement in networks regulating adaptation of the myocardium to stress. Whenever feasible, we present the results obtained in patients together with those obtained in the relevant animal and cellular models. A close examination of the findings still fails to define ANKRD1 as a negative regulator of cardiac gene expression in vivo, but rather indicates that its augmented expression can represent an adaptive response of the myocardium to stress both during development and various heart insults.

RNA-sequencing analysis reveals new alterations in cardiomyocyte cytoskeletal genes in patients with heart failure

“…Overexpression and increased protein levels of ANKRD1 in failing myocardium have been previously described, suggesting that this factor may significantly RNA-Seq and the cardiomyocyte cytoskeleton in HF I Herrer et al contribute to pathological heart remodeling. 28,29 It is surprising, however, that most investigations have focused on the induction of ANKRD1 expression in animal models and in vitro cultured primary cardiomyocytes. Thus, our study confirmed previous studies and provided accurate data about the increased ANKRD1 levels in human HF samples.…”

Identification of a Novel Gene, Anorexia, Regulating Feeding Activity via Insulin Signaling in Drosophila melanogaster

“…Based on these molecular characteristics, it is generally thought that many proteins with ankyrin repeats may play roles in integrating signals from multiple protein-protein interactions. Various kinds of ankyrin repeat-containing proteins have been identified as nuclear receptor cofactors that interact with nuclear receptors to enhance or suppress transcription of target genes (34). These reports enabled us to speculate that the Anox product may facilitate initiation of dInR transcription through interaction with dFOXO.…”

High Precision Quantitative Proteomics Using iTRAQ on an LTQ Orbitrap: A New Mass Spectrometric Method Combining the Benefits of All

“…When some prominent species of the proteins up-regulated more than 1.5-fold in the TAC model are analyzed in detail, the most pronounced hits, ANKRD1 is preferentially expressed in hearts and was previously shown to be up-regulated in response to stress and hypertrophic stimuli and in heart failure. 40 Periostin was also reported to be linked to cardiac hypertrophy due to myocardial infarction and was shown to induce proliferation of differentiated cardiomyocytes. 41 FHL1 was suggested to play an important role in biomechanical stress responses involved in cardiac hypertrophy and disease.…”