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#negative regulation

6 public questions tagged with this topic.

Paracrine Factor

Which molecule is responsible for negatively regulating Wnt signaling by removing lipid modifications?

Wnt activity modulated by extracellular modifiers controlling lipidation state and receptor availability. Notum encodes secreted carboxylesterase pectin acetylesterase-like deacylase related to lipases that specifically cleaves palmitoleate moiety added by Porcupine O-acyltransferase in ER on Wnt Ser209, essential for Frizzled binding hydrophobic groove. Removal of lipid blocks receptor engagement, dampening signal, shaping gradient. Axin and APC are intracellular negative regulators scaffolding destruction complex; Dishevelled is positive adaptor. Notum secreted from Wnt target tissue itself forms feedback inhibition loop refining gradient and preventing ectopic signaling in Drosophila wing disc and vertebrate intestinal crypt homeostasis.

Ref: Kakugawa et al., Nature 2015: Notum removes palmitoleate from Wnt inhibiting receptor binding and signaling.

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Gene regulation in Prokaryotes

Negative regulation of trp operon occurs by

Negative regulation of trp operon occurs through dual overlapping mechanisms where repressor binding directly reduces promoter activity. Active holorepressor TrpR-tryptophan complex occupies operator site overlapping transcription start site, forming high-affinity nucleoprotein complex that sterically impedes RNA polymerase holoenzyme binding and interferes with isomerization from closed to open complex. This specific interference reduces initiation frequency approximately seventyfold. Second attenuation layer further lowers productive elongation tenfold via premature termination at leader sequence. Both regulatory layers act to down-regulate biosynthetic enzyme production when end product abundant, contrasting with positive CAP-cAMP activation required for lac catabolic activation, reflecting purely repressive control of anabolic pathways.

Ref: Wikipedia trp operon – negative regulation by repressor blocking RNA polymerase, plus attenuation secondary control.

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Lac Operon

Negative regulation of lac operon occurs due to

Negative control architecture uses a repressor protein that reduces transcription when active. In lac context, lacI constitutively produces LacI repressor that occupies operator in lactose-free medium, establishing blocked state with transcription near zero. Release of negative regulator through inducer binding allows derepression. Conversely, positive regulation requires activator presence for additional stimulation beyond basal. CAP-cAMP enhances polymerase activity but does not repress, RNA polymerase is core machinery, and permease facilitates inducer import without directly contacting DNA regulatory elements. LacI therefore mediates negative regulation while CAP mediates positive regulation in this dual controlled operon.

Ref: Lodish Molecular Cell Biology - negative regulation by lac repressor; NCBI Bookshelf lac operon dual control model

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Cell Signaling ELR Pathways - I

Inhibitory Smads that negatively regulate TGF-β signaling are

Smad6/7, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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Cell Signaling ELR Pathways - I

SHP1 negatively regulates cytokine signaling by

dephosphorylating JAKs, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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Cell Signaling ELR Pathways - I

GSK-3 negatively regulates:

Glycogen synthase, is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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