Table 2.
List of Transcription Factors Known to Be Modulated by Nuclear Transport Modifiers (SN50, cSN50, cSN50.1)
| Transcription Factor* | Length (AA) | UniProt | Reference | Function |
|---|---|---|---|---|
| NFκB1 (p105 or p50) | p105: 968 p50: 433 |
P19838 | 4 | NF‐κB (nuclear factor kappa–light‐chain enhancer of activated B cells) transcription factor is a hetero‐ or homodimeric protein complex that controls transcription of >200 genes in response to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, and oxidized low‐density lipoprotein (LDL), as well as bacterial and viral antigens. NF‐κB regulates the immune response. Upregulation of NF‐κB has been linked to inflammatory and autoimmune diseases, sepsis, viral infections, disorders of immunity, and cancer, in which antiapoptotic pathways prevail in contrast to inflammation‐driven apoptosis in certain cell types. |
| Rel A (p65) | 551 | Q04206 | 4 | |
| Rel B | 579 | Q01201 | 25 | |
| c‐Rel | 619 | Q04864 | 4 | |
| NFκB2 (p100 or p52) | p100: 900 p52: 454 |
Q00653 | 25 | |
| AP‐1 (cFos/cJun) | c‐Fos: 380 c‐Jun: 331 |
P01100 P05412 |
5 | AP‐1 (activator protein 1) transcription factor is a heterodimeric protein composed of c‐Fos and c‐Jun. It regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. AP‐1 regulates cell differentiation, proliferation, and apoptosis. In some cells AP‐1 plays a proapoptotic role by regulating the expression of a specific subset of target genes that promote efficient apoptotic cell death following mitotic arrest. |
| NFATc (NFATc1) | 943 | O95644 | 5 | NFAT (nuclear factor of activated T cells) constitutes a family of transcription factors shown to be important in immune response. NFAT is also involved in the development of the cardiac, skeletal muscle, and nervous systems. The NFAT transcription factor family consists of 5 protein members: NFATc1, NFATc2, NFATc3, NFATc4, and NFAT5. |
| STAT1 | 750 | P42224 | 5 | STAT (signal transducer and activator of transcription) transcription factor regulates cell growth, differentiation, and survival. There are 7 mammalian family members: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. Dysregulation of these proteins leads to increased angiogenesis, enhanced survival of tumors, and immunosuppression. STAT proteins are also involved in the development and function of the immune system and play a role in maintaining immune tolerance and tumor surveillance. |
| Nrf2 | 605 | Q16236 | 26 | Nrf2 (nuclear factor [erythroid‐derived 2]‐like 2) transcription factor is also known as NFE2L2. Nrf2 is essential for inflammasome activation and exacerbates atherosclerosis without altering lipid metabolism (see reference 26 in the text). Nrf2 increases the expression of several antioxidant enzymes. |
| SREBP1 | Precursor: 1147 Nuclear: 490 |
P36956 | This study | SREBP (sterol regulatory element‐binding proteins) transcription factors are required for lipid homeostasis. They regulate transcription of >30 known genes that encode participants in the cholesterol, triglyceride, and fatty acid synthetic and uptake pathways. SREBPs belong to the basic‐helix–loop–helix leucine zipper class of transcription factors. Low levels of sterols induce their cleavage, forming a water‐soluble N‐terminal domain containing a bHLH‐Zip motif that is translocated to the nucleus. There are 2 distinct isoforms of SREBP1: 1a and 1c. Although SREBP‐1a regulates genes related to lipid and cholesterol synthesis and its activity is regulated by sterol levels, SREBP‐1c regulates genes required for glucose metabolism and fatty acid and lipid production. Expression of SREBP‐1c is regulated by insulin. |
| SREBP2 | Precursor: 1141 Nuclear: 484 |
Q12772 | This study | |
| ChREBP | 852 | Q9NP71 | This study | ChREBP (carbohydrate responsive element‐binding protein) transcription factor mediates activation of several regulatory enzymes of glycolysis and lipogenesis including triglyceride and fatty acid synthesis genes. |
*
Transcription factors <45 kDa are transported to the nucleus independently of importin/karyopherin alpha‐ and beta‐based pathways (see reference 27). Some of them are essential to cell survival. For example, transcription factor SFRS9 (serine/arginine‐rich splicing factor 9), also known as SRp30c or SRSF9 (≈27 kDa) is responsible for expression of >150 genes, including 50 that encode other transcription factors (see text for more details).