Description

c-Fos, also named as FOS and G0/G1 switch regulatory protein 7, is a 380 amino acid protein, which contains 1 bZIP (basic-leucine zipper) domain and belongs to the bZIP family. c-Fos is expressed at very low levels in quiescent cells. When cells are stimulated to reenter growth, c-Fos undergo 2 waves of expression, the first one peaks 7.5 minutes following FBS induction. At this stage, the c-Fos protein is localized endoplasmic reticulum. The second wave of expression occurs at about 20 minutes after induction and peaks at 1 hour. At this stage, the c-FOS protein becomes nuclear. c-Fos is a very short-lived intracellular protein, which is very easy to degrade. The calculated molecular weight of c-Fos is 40 kDa, but Phosphorylated c-Fos protein is about 60-65 kDa. It is involved in important cellular events, including cell proliferation, differentiation and survival; genes associated with hypoxia; and angiogenesis; which makes its dysregulation an important factor for cancer development. It can also induce a loss of cell polarity and epithelial-mesenchymal transition, leading to invasive and metastatic growth in mammary epithelial cells. Expression of c-Fos is an indirect marker of neuronal activity because c-Fos is often expressed when neurons fire action potentials. Upregulation of c-Fos mRNA in a neuron indicates recent activity.

Altemative Names

Activator protein 1; AP 1; C FOS; Cellular oncogene c fos; Cellular oncogene fos; FBJ murine osteosarcoma viral (v fos) oncogene homolog (oncogene FOS); FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral v fos oncogene homolog; FBJ Osteosarcoma Virus; FOS; FOS protein; FOS_HUMAN; G0 G1 switch regulatory protein 7; G0/G1 switch regulatory protein 7; G0S7; Oncogene FOS; p55; proto oncogene c Fos; Proto oncogene protein c fos; Proto-oncogene c-Fos; v fos FBJ murine osteosarcoma viral oncogene homolog

Function

Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.

PTMs

Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on both Ser-362 and Ser-374 by MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation on Ser-374 being the major site for protein stabilization on NGF stimulation. Phosphorylation on Ser-362 and Ser-374 primes further phosphorylations on Thr-325 and Thr-331 through promoting docking of MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation. Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to osteoblast transformation (By similarity).

Constitutively sumoylated with SUMO1, SUMO2 and SUMO3. Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232.

In quiescent cells, the small amount of FOS present is phosphorylated at Tyr-10 and Tyr-30 by SRC. This Tyr-phosphorylated form is cytosolic. In growing cells, dephosphorylated by PTPN2. Dephosphorylation leads to the association with endoplasmic reticulum membranes and activation of phospholipid synthesis.

Subcellular Location

Nucleus. Endoplasmic reticulum. Cytoplasm>Cytosol.

Note: In quiescent cells, present in very small amounts in the cytosol. Following induction of cell growth, first localizes to the endoplasmic reticulum and only later to the nucleus. Localization at the endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr-30.

Reactivity

Human, Mouse, Rat.

Application

IHC 1:50-1:200, IF/ICC 1:50-1:200.

Clonality

Guinea pig Polyclonal IgG

Storage

Guinea pig IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.