| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Sterols also fail to induce binding of SCAP ( L315F ) to insig 1 or insig 2 , two proteins that function in the sterol mediated retention of SREBPSCAP complexes in the endoplasmic reticulum . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Accelerated degradation is inhibited by overexpression of the sterol sensing domain of SREBP cleavage activating protein ( SCAP ) , suggesting that both proteins bind to the same site on insig 1 . ^^^ Whereas insig 1 binding to SCAP leads to ER retention , insig 1 binding to HMG CoA reductase leads to accelerated degradation that is blocked by proteasome inhibitors . ^^^ Insig 1 appears to play an essential role in the sterol mediated trafficking of two proteins with sterol sensing domains , HMG CoA reductase and SCAP . . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| In sterol treated cells , the SCAP / SREBP complex binds to Insig 1 or Insig 2 , which retains the complex in the ER , blocking SREBP processing and decreasing lipid synthesis . ^^^ Sterols block transport of the mammalian SCAP / SREBP 2 complex , but only when mammalian Insig 1 or 2 is co expressed . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Because insig 1 binds sterol regulatory element binding protein cleavage activating protein in the endoplasmic reticulum , thereby blocking proteolytic processing required for sterol regulatory element binding protein activation , we tested its influence on lipogenesis . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Crucial step in cholesterol homeostasis : sterols promote binding of SCAP to INSIG 1 , a membrane protein that facilitates retention of SREBPs in ER . ^^^ Using coimmunoprecipitation and tandem mass spectrometry , we identify INSIG 1 as an ER protein that binds the sterol sensing domain of SREBP cleavage activating protein ( SCAP ) and facilitates retention of the SCAP / SREBP complex in the ER . ^^^ Sterols induce binding of SCAP to INSIG 1 , as determined by blue native PAGE , and this is correlated with the inhibition of SCAP exit from the ER . ^^^ Mutant SCAP ( Y298C ) fails to bind INSIG 1 and is resistant to sterol mediated inhibition of ER exit . ^^^ By facilitating sterol dependent ER retention of SCAP , INSIG 1 plays a central role in cholesterol homeostasis . . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| The proteins differ functionally in two respects : ( 1 ) production of insig 1 , but not insig 2 , in cultured mammalian cells requires nuclear SREBPs ; and ( 2 ) at high levels of expression , insig 1 , but not insig 2 , can block SCAP movement in the absence of exogenous sterols . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| These findings suggest that the INSIG 1 protein alters sterol balance by modulating SREBP processing jointly with SCAP . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Insig 1 and Insig 2 , a pair of endoplasmic reticulum ( ER ) membrane proteins , mediate feedback control of cholesterol synthesis through their sterol dependent binding to the following two polytopic ER membrane proteins : sterol regulatory element binding protein ( SREBP ) cleavage activating protein ( SCAP ) and 3 hydroxy 3 methylglutaryl coenzyme A reductase . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| This in vitro inhibition is dependent on the presence of Insig 1 , an ER resident protein that is necessary for sterol mediated inhibition of Scap / SREBP transport in intact cells . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| SREBP activation is inhibited by high levels of the SREBP interacting proteins Insig 1 or the cytosolic domain of SREBP cleavage activating protein . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| More recently , Insig 1 and Insig 2 were identified as ER resident proteins that bind the SCAP / SREBP complex and promote its ER retention when cells are treated with sterols . ^^^ Insig 1 and Insig 2 also enhance the conformational change in SCAP that occurs upon addition of certain cationic amphiphiles , such as chlorpromazine , trifluoperazine , and imipramine , which mimic the effect of cholesterol . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| From the low density lipoprotein receptor to sterol regulatory element binding protein ( SREBP ) to SREBP cleavage activating protein to Insig 1 , each protein has provided a new and fundamentally novel insight into how membranes function as molecular sensors that respond to changes in the metabolic condition of the cell by moving molecules between cellular compartments . * . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Recent work has additionally uncovered integral membrane proteins , insig 1 and insig 2 , that are required to retain the SREBP SCAP complex in the ER in the presence of sterols , thus providing a more complete understanding of the control of proteolysis in this complex regulatory pathway . . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| When cellular levels of sterols rise , Insig 1 binds to the membranous sterol sensing domain of SREBP cleavage activating protein ( SCAP ) , retaining the SCAP / SREBP complex in the ER and preventing it from moving to the Golgi for proteolytic processing . ^^^ The membranous nature of Insig 1 is consistent with its sterol dependent binding to hydrophobic sterol sensing domains in SCAP and HMG CoA reductase . . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Insig 1 and Insig 2 are membrane proteins of the endoplasmic reticulum that regulate lipid metabolism by the following two actions : 1 ) sterol induced binding to 3 hydroxy 3 methylglutaryl coenzyme A reductase , an action that leads to ubiquitination and degradation of the enzyme ; and 2 ) sterol induced binding to SREBP cleavage activating protein , an action that blocks the proteolytic processing of sterol regulatory element binding proteins ( SREBPs ) , membrane bound transcription factors that enhance the synthesis of cholesterol and fatty acids . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| Insig 1 and Insig 2 are closely related proteins of the endoplasmic reticulum ( ER ) that mediate feedback control of cholesterol synthesis by sterol dependent binding to the following two membrane proteins : the escort protein Scap , thus preventing proteolytic processing of sterol regulatory element binding proteins ; and the cholesterol biosynthetic enzyme 3 hydroxy 3 methylglutaryl CoA reductase , thus inducing the ubiquitination and ER associated degradation of the enzyme . ^^^ When Asp 205 was mutated to alanine , the mutant Insig 1 lost the ability to bind to Scap and , thus , was unable to suppress the cleavage of sterol regulatory element binding proteins . ^^^ |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O15503 and Q12770 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Crucial step in cholesterol homeostasis : sterols promote binding of SCAP to INSIG 1 , a membrane protein that facilitates retention of SREBPs in ER . ^^^ Using coimmunoprecipitation and tandem mass spectrometry , we identify INSIG 1 as an ER protein that binds the sterol sensing domain of SREBP cleavage activating protein ( SCAP ) and facilitates retention of the SCAP / SREBP complex in the ER . ^^^ Sterols induce binding of SCAP to INSIG 1 , as determined by blue native PAGE , and this is correlated with the inhibition of SCAP exit from the ER . ^^^ Mutant SCAP ( Y298C ) fails to bind INSIG 1 and is resistant to sterol mediated inhibition of ER exit . ^^^ By facilitating sterol dependent ER retention of SCAP , INSIG 1 plays a central role in cholesterol homeostasis . . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| The proteins differ functionally in two respects : ( 1 ) production of insig 1 , but not insig 2 , in cultured mammalian cells requires nuclear SREBPs ; and ( 2 ) at high levels of expression , insig 1 , but not insig 2 , can block SCAP movement in the absence of exogenous sterols . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| These findings suggest that the INSIG 1 protein alters sterol balance by modulating SREBP processing jointly with SCAP . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Sterols also fail to induce binding of SCAP ( L315F ) to insig 1 or insig 2 , two proteins that function in the sterol mediated retention of SREBPSCAP complexes in the endoplasmic reticulum . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| In sterol treated cells , the SCAP / SREBP complex binds to Insig 1 or Insig 2 , which retains the complex in the ER , blocking SREBP processing and decreasing lipid synthesis . ^^^ Sterols block transport of the mammalian SCAP / SREBP 2 complex , but only when mammalian Insig 1 or 2 is co expressed . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| More recently , Insig 1 and Insig 2 were identified as ER resident proteins that bind the SCAP / SREBP complex and promote its ER retention when cells are treated with sterols . ^^^ Insig 1 and Insig 2 also enhance the conformational change in SCAP that occurs upon addition of certain cationic amphiphiles , such as chlorpromazine , trifluoperazine , and imipramine , which mimic the effect of cholesterol . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Recent work has additionally uncovered integral membrane proteins , insig 1 and insig 2 , that are required to retain the SREBP SCAP complex in the ER in the presence of sterols , thus providing a more complete understanding of the control of proteolysis in this complex regulatory pathway . . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| When cellular levels of sterols rise , Insig 1 binds to the membranous sterol sensing domain of SREBP cleavage activating protein ( SCAP ) , retaining the SCAP / SREBP complex in the ER and preventing it from moving to the Golgi for proteolytic processing . ^^^ The membranous nature of Insig 1 is consistent with its sterol dependent binding to hydrophobic sterol sensing domains in SCAP and HMG CoA reductase . . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Insig 1 and Insig 2 , a pair of endoplasmic reticulum ( ER ) membrane proteins , mediate feedback control of cholesterol synthesis through their sterol dependent binding to the following two polytopic ER membrane proteins : sterol regulatory element binding protein ( SREBP ) cleavage activating protein ( SCAP ) and 3 hydroxy 3 methylglutaryl coenzyme A reductase . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| This in vitro inhibition is dependent on the presence of Insig 1 , an ER resident protein that is necessary for sterol mediated inhibition of Scap / SREBP transport in intact cells . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Accelerated degradation is inhibited by overexpression of the sterol sensing domain of SREBP cleavage activating protein ( SCAP ) , suggesting that both proteins bind to the same site on insig 1 . ^^^ Whereas insig 1 binding to SCAP leads to ER retention , insig 1 binding to HMG CoA reductase leads to accelerated degradation that is blocked by proteasome inhibitors . ^^^ Insig 1 appears to play an essential role in the sterol mediated trafficking of two proteins with sterol sensing domains , HMG CoA reductase and SCAP . . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Insig 1 and Insig 2 are membrane proteins of the endoplasmic reticulum that regulate lipid metabolism by the following two actions : 1 ) sterol induced binding to 3 hydroxy 3 methylglutaryl coenzyme A reductase , an action that leads to ubiquitination and degradation of the enzyme ; and 2 ) sterol induced binding to SREBP cleavage activating protein , an action that blocks the proteolytic processing of sterol regulatory element binding proteins ( SREBPs ) , membrane bound transcription factors that enhance the synthesis of cholesterol and fatty acids . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| SREBP activation is inhibited by high levels of the SREBP interacting proteins Insig 1 or the cytosolic domain of SREBP cleavage activating protein . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Because insig 1 binds sterol regulatory element binding protein cleavage activating protein in the endoplasmic reticulum , thereby blocking proteolytic processing required for sterol regulatory element binding protein activation , we tested its influence on lipogenesis . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| Insig 1 and Insig 2 are closely related proteins of the endoplasmic reticulum ( ER ) that mediate feedback control of cholesterol synthesis by sterol dependent binding to the following two membrane proteins : the escort protein Scap , thus preventing proteolytic processing of sterol regulatory element binding proteins ; and the cholesterol biosynthetic enzyme 3 hydroxy 3 methylglutaryl CoA reductase , thus inducing the ubiquitination and ER associated degradation of the enzyme . ^^^ When Asp 205 was mutated to alanine , the mutant Insig 1 lost the ability to bind to Scap and , thus , was unable to suppress the cleavage of sterol regulatory element binding proteins . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| From the low density lipoprotein receptor to sterol regulatory element binding protein ( SREBP ) to SREBP cleavage activating protein to Insig 1 , each protein has provided a new and fundamentally novel insight into how membranes function as molecular sensors that respond to changes in the metabolic condition of the cell by moving molecules between cellular compartments . * . ^^^ |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q12770 and O15503 |
Pubmed |
SVM Score :0.0 |
| NA |
|