ACTB

ACTB Background

The ACTB gene provides instructions for encoding the cytoskeletal protein beta-actin, which is one of six different actin proteins and also an abundant cytoskeletal housekeeping protein. Beta-actin proteins are found in cells throughout the body. The molecular weight of ACTB is approximately 42 kDa. It plays an important role in determining cell shape and controlling cell movement (motility). Studies suggest that beta-actin may also be involved in relaying chemical signals within cells. Beta-actin has been shown to activate eNOS, thereby increasing NO production ^[1]. Recurrent mutations in this gene have been linked to cases of diffuse large B-cell lymphoma ^[2]. Due to its high conservation, beta-actin is usually used as a loading control for the integrity of cells and protein degradation in PCR and Western blotting ^[3]. The ACTB gene mutations cause Baraitser-Winter syndrome (BRWS), which is characterized by intellectual disability, cortical malformations, coloboma, sensorineural deafness, and a distinctive facial appearance in human patients ^[4]. Many biological studies suggest that a significant reduction of ACTB protein alters cell shape, migration, proliferation, and gene expression, thus leading to the detriment of brain, heart, and kidney development ^[4]. Although recurrent SERPINE1-FOSB gene fusions have been reported as the hallmark genetic abnormality in pseudomyogenic hemangioendothelioma (PHE), few cases with typical histology have this genetic alteration. Agaram NP et al. identified a novel ACTB-FOSB gene fusion in genetic alterations of pseudomyogenic hemangioendothelioma (PHE), which is rare, hardly metastasizing vascular neoplasm with a predilection to affect young adults ^[5].

[1] Kondrikov D, Fonseca FV, et al. Beta-actin association with endothelial nitric-oxide synthase modulates nitric oxide and superoxide generation from the enzyme [J]. The Journal of Biological Chemistry. Feb 2010, 285 (7): 4319-7.
[2] Lohr JG, Stojanov P, et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing [J]. Proceedings of the National Academy of Sciences of the United States of America. Mar 2012, 109 (10): 3879-4.
[3] Ruan W, Lai M. Actin, a reliable marker of internal control [J]? Clin Chim Acta. 2007 Oct;385(1-2):1-5.
[4] Cuvertino S, Stuart HM, et.al. ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder [J]. Am J Hum Genet. 2017 Dec 7;101(6):1021-1033.
[5] Agaram NP, Zhang L, et al. Expanding the Spectrum of Genetic Alterations in Pseudomyogenic Hemangioendothelioma With Recurrent Novel ACTB-FOSB Gene Fusions [J]. Am J Surg Pathol. 2018 Dec;42(12):1653-1661.