Emerging roles of the single EF-hand Ca2+ sensor tescalcin in the regulation of gene expression, cell growth and differentiation

Abstract

Tescalcin (TESC, also known as calcineurin-homologous protein 3, CHP3) is a 24-kDa EF-hand Ca2+-binding protein that has recently emerged as a regulator of cell differentiation and growth. The TESC gene has also been linked to human brain abnormalities, and high expression of tescalcin has been found in several cancers. The expression level of tescalcin changes dramatically during development and upon signal-induced cell differentiation. Recent studies have shown that tescalcin is not only subjected to up- or down-regulation, but also has an active role in pathways that drive cell growth and differentiation programs. At the molecular level, there is compelling experimental evidence showing that tescalcin can directly interact with and regulate the activities of the Na+/H+ exchanger NHE1, subunit 4 of the COP9 signalosome (CSN4) and protein kinase glycogen-synthase kinase 3 (GSK3). In hematopoetic precursor cells, tescalcin has been shown to couple activation of the extracellular signal-regulated kinase (ERK) cascade to the expression of transcription factors that control cell differentiation. The purpose of this Commentary is to summarize recent efforts that have served to characterize the biochemical, genetic and physiological attributes of tescalcin, and its unique role in the regulation of various cellular functions.

TESC Promotes TGF-α/EGFR-FOXM1-Mediated Tumor Progression in Cholangiocarcinoma

“…The sequence similarity between TESC and calcineurin B-homologous proteins 1 and 2 (CHP1 and CHP2) is substantial [27,28]. CHP1 is expressed ubiquitously in all tissues [29,30], whereas CHP2 is expressed in the small intestine and several cancers, including hepatic carcinoma, leukemia, breast cancer, and ovarian cancer [31][32][33][34][35].…”

Tescalcin promotes highly invasive papillary thyroid microcarcinoma by regulating FOS/ERK signaling pathway

“…Tescalcin (TESC), also known as calcineurin B homologous protein 3 (CHP3), was first discovered as a differentially expressed gene in the development of embryonic mouse testis [ 6 ]. Since TESC contained an EF-hand motif that is characteristic of a large family of Ca 2+ -binding proteins, it is supposed to be involved in cell growth and differentiation [ 7 ]. Previous studies have proved that abnormal expression of the TESC was associated with many types of malignant tumors including melanoma, gastric cancer, renal cell carcinoma, and colorectal cancer [ 8 – 10 ].…”

Structural and functional diversity of EF‐hand proteins: Evolutionary perspectives

“…Mielenz and Gunn‐Moore reviewed functions of swiprosin (EFHD_DM). Kolobynina et al reviewed the functions of P22 . Sole et al reviewed P22 .…”