CAND1 Antibody (Rabbit mAb) [B17D18]

Application: Reactivity: Human

Usage Information

Dilution
WB1:10000 - 1:50000 IP1:40 - 1:60 IHC1:50 - 1:100 IF1:100 - 1:250 FCM1:20

Application
WB, IP, IHC, IF, FCM

Reactivity
Human

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
136 kDa

Datasheet & SDS

Biological Description

Specificity
CAND1 Antibody (Rabbit mAb) [B17D18] detects endogenous levels of total CAND1 protein.

Clone
B17D18

Synonym(s)
KIAA0829, TIP120, TIP120A, CAND1, Cullin-associated NEDD8-dissociated protein 1, Cullin-associated and neddylation-dissociated protein 1, TBP-interacting protein of 120 kDa A, p120 CAND1, TBP-interacting protein 120A

Background
CAND1 (cullin-associated and neddylation-dissociated protein 1) is a large HEAT-repeat scaffold that binds unneddylated cullin–RING cores and dynamically controls the assembly and activity of cullin-RING ubiquitin ligases (CRLs), acting not as a static inhibitor but as a catalytic exchange factor that reshapes the repertoire of substrate receptor modules available for protein ubiquitination. The protein wraps around cullin scaffolds such as CUL1 and CUL2 in a horseshoe-like conformation, with its N‑terminal region occluding the cullin neddylation site and its C‑terminal portion occupying the adaptor-binding interface, thereby preventing simultaneous binding of SKP1–F‑box or other substrate receptor complexes and stabilizing a “core-only” state of the ligase. CAND1 binds preferentially to unneddylated CUL1–Rbx1 and blocks SCF (SKP1–CUL1–F‑box) assembly and activity, but real-time kinetic and quantitative proteomics studies have demonstrated that CAND1 catalytically accelerates F‑box module dissociation and exchange by orders of magnitude once CSN-mediated deneddylation has occurred, driving rapid equilibration of CUL1–Rbx1 cores with diverse SKP1–F‑box pairs and ensuring comprehensive sampling of available substrate receptors. In this adaptive cycle, substrate binding promotes Nedd8 conjugation to CUL1, which displaces CAND1 and stabilizes an active SCF complex until the substrate is ubiquitinated and degraded; subsequent CSN deneddylation reopens the cullin for CAND1 binding, and CAND1 then disassembles the existing adaptor complex and facilitates recruitment of alternative F‑box modules, coupling neddylation status to substrate-receptor turnover and maintaining plasticity in CRL1 signaling. For CUL2-based CRL2^VHL ligases involved in PROTAC target degradation, CAND1 dramatically increases dissociation of CRL2 complexes but only weakly promotes reassembly, thereby inhibiting CRL2-mediated protein degradation and highlighting family- and context-specific effects of CAND1 on distinct CRLs. CAND1 functions as a positive regulator of cullin-containing E3s in vivo, supporting optimal activity of SCF^SLY1^ in gibberellin signaling and cooperating with COP1/COP10 and CUL4 complexes to promote HY5 degradation and repress photomorphogenesis, tuning multiple cullin platforms rather than acting as a simple off-switch. By governing CRL1 composition, CAND1 influences degradation of key regulators in cell-cycle progression, hormone and growth factor pathways, and stress responses, and its dysregulation perturbs normal proteolytic trajectories, affecting metabolic and regenerative phenotypes. In nonalcoholic fatty liver disease, CAND1 is downregulated during hepatic steatosis, enhancing assembly of CUL1–FBXO42–ACAA2 complexes and accelerating ubiquitination and degradation of the mitochondrial β‑oxidation enzyme ACAA2, reducing fatty acid catabolism and promoting lipid accumulation, whereas restoring CAND1 function blocks this assembly and alleviates NAFLD. In adult heart regeneration, elevated CAND1 expression promotes assembly of CUL1–FBXW11–Mob1b complexes and K48-linked ubiquitination of Mob1b, suppressing Hippo signaling and facilitating cardiomyocyte proliferation and repair after myocardial infarction, illustrating how CAND1-directed CRL1 remodeling can be harnessed to manipulate major growth-control pathways. The HEAT-repeat scaffold structure, dual engagement of cullin neddylation and adaptor interfaces, catalytic exchange-factor mechanism, and demonstrated roles in maintaining dynamic CRL repertoires, tuning hormone and light signaling, and modulating Hippo and metabolic pathways position CAND1 as a mechanistically central regulator for ubiquitin-proteasome–based control of signaling, metabolic and regenerative pathologies, and for implementing CRL-targeted interventions.

Background

CAND1 (cullin-associated and neddylation-dissociated protein 1) is a large HEAT-repeat scaffold that binds unneddylated cullin–RING cores and dynamically controls the assembly and activity of cullin-RING ubiquitin ligases (CRLs), acting not as a static inhibitor but as a catalytic exchange factor that reshapes the repertoire of substrate receptor modules available for protein ubiquitination. The protein wraps around cullin scaffolds such as CUL1 and CUL2 in a horseshoe-like conformation, with its N‑terminal region occluding the cullin neddylation site and its C‑terminal portion occupying the adaptor-binding interface, thereby preventing simultaneous binding of SKP1–F‑box or other substrate receptor complexes and stabilizing a “core-only” state of the ligase. CAND1 binds preferentially to unneddylated CUL1–Rbx1 and blocks SCF (SKP1–CUL1–F‑box) assembly and activity, but real-time kinetic and quantitative proteomics studies have demonstrated that CAND1 catalytically accelerates F‑box module dissociation and exchange by orders of magnitude once CSN-mediated deneddylation has occurred, driving rapid equilibration of CUL1–Rbx1 cores with diverse SKP1–F‑box pairs and ensuring comprehensive sampling of available substrate receptors. In this adaptive cycle, substrate binding promotes Nedd8 conjugation to CUL1, which displaces CAND1 and stabilizes an active SCF complex until the substrate is ubiquitinated and degraded; subsequent CSN deneddylation reopens the cullin for CAND1 binding, and CAND1 then disassembles the existing adaptor complex and facilitates recruitment of alternative F‑box modules, coupling neddylation status to substrate-receptor turnover and maintaining plasticity in CRL1 signaling. For CUL2-based CRL2^VHL ligases involved in PROTAC target degradation, CAND1 dramatically increases dissociation of CRL2 complexes but only weakly promotes reassembly, thereby inhibiting CRL2-mediated protein degradation and highlighting family- and context-specific effects of CAND1 on distinct CRLs. CAND1 functions as a positive regulator of cullin-containing E3s in vivo, supporting optimal activity of SCF^SLY1^ in gibberellin signaling and cooperating with COP1/COP10 and CUL4 complexes to promote HY5 degradation and repress photomorphogenesis, tuning multiple cullin platforms rather than acting as a simple off-switch. By governing CRL1 composition, CAND1 influences degradation of key regulators in cell-cycle progression, hormone and growth factor pathways, and stress responses, and its dysregulation perturbs normal proteolytic trajectories, affecting metabolic and regenerative phenotypes. In nonalcoholic fatty liver disease, CAND1 is downregulated during hepatic steatosis, enhancing assembly of CUL1–FBXO42–ACAA2 complexes and accelerating ubiquitination and degradation of the mitochondrial β‑oxidation enzyme ACAA2, reducing fatty acid catabolism and promoting lipid accumulation, whereas restoring CAND1 function blocks this assembly and alleviates NAFLD. In adult heart regeneration, elevated CAND1 expression promotes assembly of CUL1–FBXW11–Mob1b complexes and K48-linked ubiquitination of Mob1b, suppressing Hippo signaling and facilitating cardiomyocyte proliferation and repair after myocardial infarction, illustrating how CAND1-directed CRL1 remodeling can be harnessed to manipulate major growth-control pathways. The HEAT-repeat scaffold structure, dual engagement of cullin neddylation and adaptor interfaces, catalytic exchange-factor mechanism, and demonstrated roles in maintaining dynamic CRL repertoires, tuning hormone and light signaling, and modulating Hippo and metabolic pathways position CAND1 as a mechanistically central regulator for ubiquitin-proteasome–based control of signaling, metabolic and regenerative pathologies, and for implementing CRL-targeted interventions.

References
https://pubmed.ncbi.nlm.nih.gov/38177676/ https://pubmed.ncbi.nlm.nih.gov/23535663/

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%