Sterol regulatory element-binding protein

Sterol regulatory element-binding transcription factor 1
X-ray crystallography of Sterol Regulatory Element Binding Protein 1A with polydeoxyribonucleotide.
Identifiers
Symbol	SREBF1
Entrez	6720
HUGO	11289
OMIM	184756
PDB	1am9
RefSeq	NM_004176
UniProt	P36956
Other data
Locus	Chr. 17 p11.2

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop.

Mammalian genomes have two separate SREBP genes (SREBF1 and SREBF2):

SREB proteins are indirectly required for cholesterol biosynthesis and for uptake and fatty acid biosynthesis. These proteins work with asymmetric sterol regulatory element (StRE). SREBPs have a structure similar to E-box-binding helix-loop-helix (HLH) proteins. However, in contrast to E-box-binding HLH proteins, an arginine residue is replaced with tyrosine making them capable of recognizing StREs and thereby regulating membrane biosynthesis.

Animal cells maintain proper levels of intracellular lipids (fats and oils) under widely varying circumstances (lipid homeostasis). For example, when cellular cholesterol levels fall below the level needed, the cell makes more of the enzymes necessary to make cholesterol. A principal step in this response is to make more of the mRNA transcripts that direct the synthesis of these enzymes. Conversely, when there is enough cholesterol around, the cell stops making those mRNAs and the level of the enzymes falls. As a result, the cell quits making cholesterol once it has enough.