Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''SREBF1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. This gene is located within the

Smith–Magenis syndrome Smith–Magenis Syndrome (SMS), also known as 17p- syndrome, is a microdeletion syndrome characterized by an abnormality in the short (p) arm of chromosome 17. It has features including intellectual disability, facial abnormalities, difficulty s ...

region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene. The isoforms are SREBP-1a and SREBP-1c (the latter also called ADD-1). SREBP-1a is expressed in the intestine and spleen, whereas SREBP-1c is mainly expressed in liver, muscle, and fat (among other tissues).

Expression

The proteins encoded by this gene are

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...

that bind to a sequence in the promoter of different genes, called sterol regulatory element-1 (SRE1). This element is a decamer (

oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relati ...

with ten subunits) flanking the

LDL receptor The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor t ...

gene and other genes involved in, for instance, sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ...

. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper ( bHLH-Zip) transcription factor family. SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell. SREBP-1a and SREBP-1c are both encoded by the same gene, but are transcribed by different promoters. For animals in a fasted state, SREBP-1c expression is suppressed in the liver, but a high carbohydrate meal (by insulin release) strongly induces SREBP-1c expression.

Function

SREBP-1 plays a key role in the induction of

lipogenesis In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride s ...

by the liver. mTORC1 is activated by

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...

(a hormone of nutrient abundance) leading to increased production of SBREP-1c, which facilitates storage of fatty acids (excess nutrients) as

triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as ...

Clinical relevance

SREBP-1c regulates genes required for glucose metabolism and fatty acid and lipid production and its expression is induced by insulin.

Insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism ...

-stimulated SREBP-1c increases

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...

by activation of

glucokinase Glucokinase () is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in t ...

enzyme, and increases

(conversion of carbohydrates into fatty acids). Insulin stimulation of SREBP-1c is mediated by

liver X receptor The liver X receptor (LXR) is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors (LXRs) are important regulators of cholesterol, ...

(LXR) and mTORC1. High blood levels of insulin due to

insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood sugar ...

often leads to

steatosis Steatosis, also called fatty change, is abnormal retention of fat (lipids) within a cell or organ. Steatosis most often affects the liver – the primary organ of lipid metabolism – where the condition is commonly referred to as fatty liver disea ...

in the liver because of SREBP-1 activation. Suppression of SREBP-1c by

sirtuin 1 Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 ('' S. cerevisiae''), referring to the fact ...

or by other means protects against development of fatty liver. SREBP-1 is highly activated in cancers because tumor cells require lipids for cell membranes,

second messengers Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first m ...

, and energy.

Interactions

SREBF1 has been shown to

interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...

with: *

CREB-binding protein Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intri ...

, *

DAX1 DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) is a nuclear receptor protein that in humans is encoded by the ''NR0B1'' gene (nuclear receptor subfamily 0, group B, member 1). The ''NR0B1'' gene i ...

LMNA Pre-lamin A/C or lamin A/C is a protein that in humans is encoded by the ''LMNA'' gene. Lamin A/C belongs to the lamin family of proteins. Function In the setting of ZMPSTE24 deficiency, the final step of lamin processing does not occur, r ...

, and *

TWIST2 Twist-related protein 2 is a protein that in humans is encoded by the ''TWIST2'' gene. The protein encoded by this gene is a basic helix-loop-helix (bHLH) transcription factor and shares similarity with another bHLH transcription factor, TWIST1. ...

. * BHLHE40 * BHLHE41

References

External links

* * {{Transcription factors and intracellular receptors, g1 Transcription factors