Expression of SET is modulated as a function of cell proliferation

Abstract

We explored a biological role of SET as it relates to cell proliferation and differentiation. Immunohistochemical staining demonstrated that the expression of SET was ubiquitous and diffuse over the whole embryo on gestational day 15. At a later stage of development, SET was expressed at relatively lower levels and localized to specific tissues and cells. On embryonic day 19, specific SET immunoreactivity was found in the epithelium of skin, respiratory tract, intestine, and retina as well as in muscle and cartilage. In these cells SET was stained mostly in the nucleus, which was supported indirectly by nuclear transport of enhanced green fluorescence protein-SET fusion proteins in ECV304 endothelial cells. Set mRNA expression was further confirmed in various cultured cells, including NIH 3T3 cells, L6 myoblast cells, human umbilical vein endothelial cells, and ECV304 cells. Using F9 teratocarcinoma cell lines, which were stimulated to differentiate into the two different cell lineages of parietal and visceral endoderm, we have further examined the role of SET. The expression of set mRNA and SET protein was diminished about three-fold in both differentiated endoderm cells compared to the undifferentiated F9 cells. However, when F9 cells were subjected to serum starvation, reduction of set mRNA abundance also took place at a similar level to that observed in response to differentiation. Consistent with this, quiescent L6 myoblast showed a marked downregulation of set mRNA compared to proliferating cells. These results suggest that SET is involved mainly in the regulation of cell proliferation rather than differentiation during embryonic development.

Cytoplasmic Retention of Protein Phosphatase 2A Inhibitor 2 (I2PP2A) Induces Alzheimer-like Abnormal Hyperphosphorylation of Tau

“…, also known as SET␣, TAF-1␤, and PHAPII, is a nuclear protein that regulates cell cycle (21), cell proliferation (22), and cell motility (23). Moreover, I 2 PP2A controls gene transcription (24) by regulating histone acetylation (25) and is possibly involved in neuronal apoptotic pathways in AD brain (26).…”

Zinc Finger and X-Linked Factor (ZFX) Binds to Human SET Transcript 2 Promoter and Transactivates SET Expression

“…Accumulated data have shown that, through PP2A-dependant and PP2A-independent pathways, SET plays a critical role in the cell cycle regulation and contributes to the development of hematological malignancies and solid tumors, especially gynecologic cancers [13,14]. In breast cancers, SET overexpression is a frequent molecular event associated with shorter overall and disease-free survival of patients [15].…”

The Role of the Y-Located TSPY Gene in Prostatic Oncogenesis

“…TSPY harbors a cyclin B binding domain, similar to those of SET oncogene and nucleosome assembly proteins (NAP) (Tsuchiya et al, 1995;Schnieders et al, 1996;Lau, 1999). Some members of this protein family are involved in either regulating or modulating cell cycle progression (Altman and Kellogg, 1997;Shin et al, 1999;Chai et al, 2001;Canela et al, 2003;Pandey et al, 2003). It is uncertain what effects TSPY might have when it is aberrantly expressed in cells and/or tissues incapable of entering male meiosis.…”