An FF Domain-Dependent Protein Interaction Mediates a Signaling Pathway for Growth Factor-Induced Gene Expression

Jiang, Wei; Sordella, Raffaella; Chen, Guang-Chao; Hakre, Shweta; Roy, Ananda L.; Settleman, Jeffrey

doi:10.1016/j.molcel.2004.11.024

Cited by 58 publications

(83 citation statements)

References 26 publications

(1 reference statement)

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“…Consistent with these observations TFII-I was found to be constitutively nuclear in p190 null cells, resulting in an enhanced c-fos transcription in response to growth factors. Most importantly, ectopic expression of p190 rescued both cytoplasmic localization of TFII-I and subsequent downregulation of c-fos (36). These results suggest that regulated association of TFII-I with p190RhoGAP in the cytoplasm is an important step in mitogen-induced transcription regulation of c-fos, although the precise involvement and contribution of individual isoforms of TFII-I in the p190 RhoGAP pathway is not yet determined.…”

Section: Role Of Tfii-i In Rho/gap Pathwaymentioning

confidence: 89%

“…The integrity of Y248 is also required for interaction with MAPK, suggesting that tyrosine phosphorylation of TFII-I is critical for its downstream function (35). Intriguingly, TFII-I is downstream of both the Ras and Rho pathways, raising the possibility that besides SRF and Elk-1, TFII-I could provide the necessary regulatory input for c-fos activation (36).…”

Section: Transcriptional Regulation Of C-fos By Tfii-imentioning

confidence: 99%

“…Subcellular staining indicated that the TFII-IΔ isoform exhibits a predominantly cytoplasmic localization in serum-starved cells (32). Growth factor signaling leads to rapid tyrosine phosphorylation and nuclear translocation of TFII-IΔ in murine fibroblasts, which is necessary for the transcriptional activation of c-fos (28,36). However, in addition to the Δ-isoform, murine fibroblasts also express the β-isoform.…”

Section: Opposing Action Of Tfii-i Isoforms Regulate C-fos Transcriptionmentioning

confidence: 99%

“…The p190RhoGAP proteins are potent Rho inhibitors, which are implicated in the regulation of Rho-dependent cytoskeletal reorganization and subsequent transcriptional activation in response to mitogens (19,20). In a search for proteins that might interact with p190RhoGAP, TFII-I was identified as an interacting partner of the p190A RhoGAP protein (36). The interaction was mediated via the FF-domain in p190RhoGAP and the N-terminal 90 amino acids in TFII-I (36).…”

Section: Role Of Tfii-i In Rho/gap Pathwaymentioning

confidence: 99%

“…The interaction was mediated via the FF-domain in p190RhoGAP and the N-terminal 90 amino acids in TFII-I (36). Although FF domains are usually present in splicing and transcription factors, utilization of FF domains for signal-induced transcriptional regulation was not known (36). Stimulation through the PDGF receptor resulted in tyrosine phosphorylation of TFII-I and its subsequent release from p190RhoGAP to activate c-fos.…”

Section: Role Of Tfii-i In Rho/gap Pathwaymentioning

confidence: 99%

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Signal-induced functions of the transcription factor TFII-I

Roy

2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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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.

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Section: Role Of Tfii-i In Rho/gap Pathwaymentioning

confidence: 89%

Section: Transcriptional Regulation Of C-fos By Tfii-imentioning

confidence: 99%

Section: Opposing Action Of Tfii-i Isoforms Regulate C-fos Transcriptionmentioning

confidence: 99%

Section: Role Of Tfii-i In Rho/gap Pathwaymentioning

confidence: 99%

Section: Role Of Tfii-i In Rho/gap Pathwaymentioning

confidence: 99%

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Signal-induced functions of the transcription factor TFII-I

Roy

2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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HNRNPL Circularizes ARHGAP35 to Produce an Oncogenic Protein

et al. 2021

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Circular RNAs (circRNAs) are an intriguing class of widely prevalent endogenous RNAs, the vast majority of which have not been characterized functionally. Here, we identified a novel oncogenic circRNA originating from the back-splicing of Exon2 and Exon3 of a tumor suppressor gene, ARHGAP35 (also known as P190-A), termed as circARHGAP35. have observe that circARHGAP35 and linear ARHGAP35 have antithetical expression and functions. Interestingly, circARHGAP35 contains a 3867 nt long ORF with an m 6 A-modified start codon and encodes a truncated protein comprising four FF domains and lacking the Rho GAP domain. Mechanistically, circARHGAP35 protein promotes cancer cell progression by interacting with TFII-I protein in the nucleus. The RNA binding protein, HNRNPL, facilitates the formation of circARHGAP35. Clinically, circARHGAP35 is associated with poor survival in cancer patients. Our findings characterize an oncogenic circRNA and demonstrate a novel mechanism of oncogene activation in cancer by circRNA through the production of a truncated protein.

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Solution structure of the yeast URN1 splicing factor FF domain: Comparative analysis of charge distributions in FF domain structures—FFs and SURPs, two domains with a similar fold

2008

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FF domains are present in three protein families: the splicing factors formin binding protein 11 (FBP11), Prp40, and URN1, the transcription factor CA150, and the p190RhoGTPase-related proteins. This simplicity in distribution, however, is contrasted by the difficulty in defining their biological role. At best, the group of ligand FF domains can bind to form a motley crew with binding reports pointing also to negative/aromatic sequences, the tetratricopeptide repeat, the transcription factor TFII-I and even to RNA. To expand our knowledge on the FF domain, we selected the FF domain present in the URN1 yeast splicing factor as the subject for structural studies. The URN1 protein is one of the two known proteins containing only one FF domain, making it the most simplified representative of FF domain-containing splicing factors. The solution structure reveals that the domain adopts the classical FF fold, with a distinctive negatively charged patch on its surface. All available FF structures have a well-conserved fold but variable electrostatic patches on their surfaces. These patches are unconserved, even for domains with similar pK(a)s. To investigate potential binding sites in FF domains, we performed structural comparisons to other proteins with similar folds. In addition to the structures detected by SCOP, we included SURP domains, which also adopt the alpha1-alpha2-3(10)-alpha3 architecture. We observed that the main difference between all these structures resides in the orientation of the second helix. Remarkably, in DEK, SURP, and Prp40FF1 structures (the exception is the FBP11FF1 domain), the second helix participates in ligand recognition. Furthermore, SURP and Prp40FF1 binding sites also include the 3(10) helix, which forms a partially exposed hydrophobic cavity. This cavity is also present in at least CA150FF1 and FF2 structures. Thus, as with WW domains, the FF fold seems to have developed binding-site variations to accommodate an abundant and variable set of ligands.

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An FF Domain-Dependent Protein Interaction Mediates a Signaling Pathway for Growth Factor-Induced Gene Expression

Cited by 58 publications

References 26 publications

Signal-induced functions of the transcription factor TFII-I

Signal-induced functions of the transcription factor TFII-I

HNRNPL Circularizes ARHGAP35 to Produce an Oncogenic Protein

Solution structure of the yeast URN1 splicing factor FF domain: Comparative analysis of charge distributions in FF domain structures—FFs and SURPs, two domains with a similar fold

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