Function and expression of ATIP and its variants in cardiomyoblast cell line H9c2

Abstract

Previously ATIP has been shown to inhibit growth factor signalling in cancerous cells via an interaction with the AT2-receptor. This is the first report to identify that ATIP may have a similar role in other disease states characterised by excessive growth and indicates that for ATIP3, at least, an interaction with the AT2-receptor may not be necessary.

Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

“…All of these transcripts share a common 118 amino acid AT2-receptor interacting domain (ID), which suggests that all 5 MTUS1 transcripts interact with the AT2-receptor and induce atypical signal transduction pathways including at least three intracellular cascades involving protein phosphatase activation, nitric oxide regulation, and phospholipase A2 stimulation (Knowle et al, 2000). Additionally, recent studies have shown that MTUS1 loss or downregulation is associated with enhanced tumor proliferation, poor tumor differentiation, and poor prognosis in bladder cancer (Xiao et al, 2012), gastric cancer (Li et al, 2014a), salivary adenoid cystic carcinoma (Zhao et al, 2015), and other cancers (Louis et al, 2010; Louis et al, 2011; Ding et al, 2012; Varghayee et al, 2015). In addition, MTUS1 has been shown to interfere with activation of the ERK2 pathway and to inhibit proliferation of cells stimulated with growth factors, such as insulin, bFGF, PDGF, and EGF (Nouet et al, 2004; Zuern et al, 2010).…”

MDM4 (Murine Double Minute 4)

“…Recent reports indicate that MTUS1/ATIP may inhibit growth factor signaling not only in cancer but in other disease states characterized by excessive growth. For instance, the MTUS1/ATIP variants are abundantly expressed in cultured cardio-myoblast and myotubules and there is evidence to suggest that isoform1/ATIP3A may play an antiproliferative and antihypertrophic role in these cells in the absence of AT2-receptor expression or activation (Varghayee et al 2015). Further evidence that supports a role for MTUS1/ ATIP in the development of cardiac disease comes in the form of a report which describes the development of MTUS1 knockout mice, which develop normally but reveal higher body weights and slightly decreased blood pressure levels.…”

Mgc39955

“…RHEB phosphorylation at S130 was shown to be mediated by MK5 (Zheng et al 2011) and MK5 was also reported to be the kinase responsible for S37 phosphorylation of p53, downstream to oncogenic Ras-p38 signaling (Sun et al 2007). In addition, independent studies have shown a role for MK5 in the phosphorylation of the fork-head family transcription factors FOXO1 and FOXO3a at a conserved residue (S215) in the DNA-binding domain (Kress et al 2011;Chow et al 2013).…”