FHL1 BASIC INFORMATION
| Standard Name | FHL1 1 |
|---|---|
| Systematic Name | YPR104C |
| Alias | SPP42 2 , 3 |
| Feature Type | ORF, Verified |
| Description | Transcriptional activator with similarity to DNA-binding domain of Drosophila forkhead but unable to bind DNA in vitro; isolated as suppressor of RNA polymerase III mutant and of splicing factor prp4 (1, 2, 4 and see Summary Paragraph)
|
| Name Description | Fork Head-Like 1 |
| GO Annotations | All FHL1 GO evidence and references |
|---|---|
| View Computational GO annotations for FHL1 | |
| Molecular Function | |
| Manually curated | |
| High-throughput | |
| Biological Process | |
| Manually curated | |
| Cellular Component | |
| Manually curated |
| Regulatory Role | |
|---|---|
| Binding motifs | FHL1 Transcription Factor Binding Sites and References |
| |
| Regulatory modules | predicted: stressResponse ( 559 , 553 ) |
| Mutant Phenotype | All FHL1 Phenotype details and references |
|---|---|
| Classical genetics | |
| conditional | |
| null |
|
| Large-scale survey | |
| null |
| Interactions | FHL1 All interactions details and references |
|---|---|
| 37 total interaction(s) for 28 unique genes/features. | |
| Physical Interactions |
|
| Genetic Interactions |
|
| External Links | All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB |
|---|
| Primary SGDID | S000006308 |
|---|
ADDITIONAL INFORMATION for FHL1
SUMMARY PARAGRAPH for FHL1
Originally isolated as a suppressor of Pol III mutations, FHL1 encodes a transcriptional activator that is involved in the expression of ribosomal protein (RP) genes (1, 5, and reviewed in 6). Fhl1p localizes to promoters of RP genes but it is still unclear whether this is through direct binding with DNA, as it has sequence similarity to the DNA-binding domain of the Drosophila forkhead protein (7, 1), or whether it is an indirect association dependent on the DNA-binding abilities of proteins such as Rap1p and Hmo1p, since in vitro studies show a lack of Fhl1p/DNA interaction (4, 8, 9). Fhl1p is also loosely associated with the CURI complex, which is involved in the transcription of ribosomal genes (10). Null mutations of FHL1 result in a severely reduced growth rate with cells having only 20% the normal amount of RNA and able to synthesize ribosomes at 5-10% the rate of wild-type cells (1, 4).
Fhl1p is regulated through a complex mechanism that involves the TOR pathway, the coactivator Ifh1p, and the corepressor Crf1p (11). Under conditions of growth, the TOR signaling pathway represses Yak1p kinase activity thus maintaining Crf1p in an inactive state in the cytoplasm. In the absence of Crf1p, Ifh1p is able to bind to the forkhead-associated (FHA) domain of Fhl1p and activate transcription of the RP genes (7, 4). When the TOR pathway is inactive, Yak1p repression is released, enabling the kinase to phosphorylate and activate Crf1p. Phosphorylated Crf1p localizes to the nucleus and binds to Fhl1p, thus displacing Ifh1p and consequently shutting off RP gene transcription (11).
The FHA domain of Fhl1p is similar in sequence to FHA domains found in other transcription factors such as S. cerevisiae Fkh1p, Fkh2p, and Hcm1p as well as S. pombe FHL1, tobacco NtFHA1, and the mammalian HNF-3 family (1, 12, 13).
REFERENCES CITED ON THIS PAGE [View Complete Literature Guide for FHL1]
| 1) | Hermann-Le Denmat S, et al. (1994) Suppression of yeast RNA polymerase III mutations by FHL1, a gene coding for a fork head protein involved in rRNA processing. Mol Cell Biol 14(5):2905-13 |
| 2) | Maddock JR, et al. (1994) Extragenic suppressors of Saccharomyces cerevisiae prp4 mutations identify a negative regulator of PRP genes. Genetics 136(3):833-47 |
| 3) | Maddock J (1990) Genetic interactions among yeast gene products required for messenger RNA processing. Ph.D. thesis, Carnegie Mellon University, United States |
| 4) | Rudra D, et al. (2005) Central role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteins. EMBO J 24(3):533-42 |
| 5) | Schawalder SB, et al. (2004) Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1. Nature 432(7020):1058-61 |
| 6) | Inoki K and Guan KL (2006) Complexity of the TOR signaling network. Trends Cell Biol 16(4):206-12 |
| 7) | Wade JT, et al. (2004) The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes. Nature 432(7020):1054-8 |
| 8) | Zhao Y, et al. (2006) Fine-structure analysis of ribosomal protein gene transcription. Mol Cell Biol 26(13):4853-62 |
| 9) | Hall DB, et al. (2006) An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes and throughout the rRNA gene locus in Saccharomyces cerevisiae. Mol Cell Biol 26(9):3672-9 |
| 10) | Rudra D, et al. (2007) Potential interface between ribosomal protein production and pre-rRNA processing. Mol Cell Biol 27(13):4815-24 |
| 11) | Martin DE, et al. (2004) TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell 119(7):969-79 |
| 12) | Szilagyi Z, et al. (2005) Characterisation of two novel fork-head gene homologues of Schizosaccharomyces pombe: their involvement in cell cycle and sexual differentiation. Gene 348:101-9 |
| 13) | Kim M, et al. (2002) Forkhead-associated domains of the tobacco NtFHA1 transcription activator and the yeast Fhl1 forkhead transcription factor are functionally conserved. J Biol Chem 277(41):38781-90 |






