Signal-induced functions of the transcription factor TFII-I

Abstract

We have learned a great deal over the last several years about the molecular mechanisms that govern cell growth, cell division and cell death. Normal cells pass through cell cycle (growth) and divide in response to mitogenic signals that are transduced through their cognate cell surface receptors to the nucleus. Despite the fact that cellular growth and division are mechanistically distinct steps, they are usually coordinately regulated, which is critical for normal cellular proliferation. The precise mechanistic basis for this coordinated regulation is unclear. TFII-I is a unique, signal induced multifunctional transcription factor that is activated upon a variety of signaling pathways and appears to participate in distinct phases of cell growth. For instance, TFII-I is required for growth factorinduced transcriptional activation of the c-fos gene, which is essential for cell cycle entry. Two alternatively spliced isoforms of TFII-I exhibit opposing but necessary functions for mitogen-induced transcriptional activation of c-fos. Besides transcriptional activation of the c-fos proto-oncogene and eventual entry into cell cycle, TFII-I also appears to have a role in later phases of the cell cycle and cell division. Here we discuss how a multitude of signaling inputs target TFII-I isoforms, which may exert their functions in distinct phases of the cell cycle and play a key role in the coordinated regulation of cellular proliferation.

Sterol Regulatory Element-Binding Protein 2 Couples HIV-1 Transcription to Cholesterol Homeostasis and T Cell Activation

“…TFII-I is a widely expressed transcription factor that plays an important role in cellular calcium homeostasis and the transcriptional regulation of genes involved in cell cycle progression, endoplasmic reticulum stress response, angiogenesis, and embryonic development (9,25). TFII-I is also an important component of a transcription factor complex that regulates LTR-driven transcription of HIV genes (26).…”

Role of Helix-Loop-Helix Proteins during Differentiation of Erythroid Cells

“…Haploinsufficiency associated with this genomic region causes Williams-Beuron syndrome (WBS), a disease affecting the development of the neuronal system (108,109). Recently, the Roy and Bayarsaihan laboratories generated mice with targeted deletions of the gene for TFII-I (Gtf2i) and the gene for the related protein Gtf2ird (34).…”

“…TFII-I has three different isoforms (alpha, beta, and delta) that are generated by alternative splicing (108,109). In serumstarved cells, the beta isoform was shown to associate with the c-fos promoter and to keep the promoter accessible while in an inactive state (49).…”

“…The activity of TFII-I is regulated by signal transduction pathways (109), and like USF, it activates the expression of cell cycle regulators, including cyclin D1 and protein kinase C-␤, thus mediating cell cycle progression through the G 1 -to-S and G 2 -to-M phases of the cell cycle (4). TFII-I is phosphorylated at tyrosine residues, which regulates its abilities to relocate to the nucleus and to interact with specific proteins (19,96,149).…”

Identification of the TFII-I family target genes in the vertebrate genome

“…T FII-I proteins represent a ubiquitously expressed versatile protein family with broad functional activities (1)(2)(3)(4)(5)(6)(7). GTF2I and GTF2IRD1 are localized in the 7q11.23 chromosomal region, deletion of which causes the Williams syndrome, a complex developmental disorder characterized by cardiac, craniofacial, behavioral, and cognitive anomalies (8)(9)(10)(11).…”