Product Details

Uniprot No.

Target Names

DTL

Alternative Names

Denticleless protein homolog (DDB1- and CUL4-associated factor 2) (Lethal(2) denticleless protein homolog) (Retinoic acid-regulated nuclear matrix-associated protein), DTL, CDT2 CDW1 DCAF2 L2DTL RAMP

Species Reactivity

Human

Immunogen

A synthesized peptide from human DTL protein

Immunogen Species

Homo sapiens (Human)

Conjugate

Non-conjugated

Clonality

Monoclonal

Isotype

Rabbit IgG

Clone No.

3E8

Purification Method

Affinity-chromatography

Concentration

It differs from different batches. Please contact us to confirm it.

Buffer

Rabbit IgG in 10mM phosphate buffered saline , pH 7.4, 150mM sodium chloride, 0.05% BSA, 0.02% sodium azide and 50% glycerol.

Form

Liquid

Tested Applications

ELISA, IHC, IF, FC

Recommended Dilution

Application	Recommended Dilution
IHC	1:50-1:200
IF	1:50-1:200
FC	1:50-1:200

Protocols

ELISA Protocol
Immunohistochemistry (IHC) Protocol
Immunofluorescence (IF) Protocol
Flow Cytometry (FC) Protocol

Troubleshooting and FAQs

Antibody FAQs

Storage

Upon receipt, store at -20°C or -80°C. Avoid repeated freeze.

Lead Time

Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time maybe differs from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

Description

DTL, also known as Denticleless protein homolog or DCAF2, serves as a critical substrate receptor for the CUL4-DDB1 E3 ubiquitin ligase complex, playing essential roles in cell cycle regulation and DNA damage response pathways. This protein facilitates the targeted degradation of key cell cycle regulators, making it a significant focus for researchers investigating ubiquitin-mediated proteolysis, replication licensing, and genomic stability mechanisms.

This recombinant monoclonal antibody, clone 3E8, offers the reproducibility and consistency that demanding experimental workflows require. Developed using recombinant technology with a sequence-defined approach, this rabbit IgG antibody eliminates the lot-to-lot variability often encountered with traditional hybridoma-derived reagents, ensuring your results remain comparable across extended studies and collaborative projects.

Validation across multiple detection platforms demonstrates this antibody's versatility in your research toolkit. Immunohistochemistry studies using human placenta tissue sections show clear target detection at dilutions of 1:100, with citrate buffer antigen retrieval providing optimal results on paraffin-embedded samples. Immunofluorescence analysis in HeLa cells reveals specific staining patterns at 1:50 dilution, while flow cytometry experiments using Jurkat cells demonstrate distinct positive population shifts compared to isotype controls, confirming reliable performance in suspension cell analysis.

The antibody arrives in a stabilized liquid format containing glycerol for convenient long-term storage at -20°C or -80°C, ready for immediate use without reconstitution. Affinity chromatography purification ensures high purity suitable for sensitive downstream applications.

Whether investigating cell cycle checkpoint mechanisms, exploring CUL4-DDB1 complex biology, or examining DNA damage response pathways, this DTL antibody provides the validated performance and experimental flexibility needed to advance your research with confidence.

Usage

For Research Use Only. Not for use in diagnostic or therapeutic procedures.

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Target Background

Function

Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2. CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis. The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1.

Gene References into Functions

Results suggest that CDK-mediated phosphorylation of Cdt2 inactivates its ubiquitin ligase activity by reducing its affinity to PCNA, an important strategy for regulating the levels of key proteins in the cell cycle. PMID: 29424068
Findings suggest that DTL overexpression plays a crucial role in tumor cell proliferation in gastric carcinoma. PMID: 26472028
CDT2 mediated XPG elimination from DNA damage sites clears the chromatin space needed for repair. PMID: 25483071
CDT2 likely is a non-oncogene to which transformed cells become addicted because of their enhanced cellular stress, such as replicative stress and DNA damage. PMID: 25115388
These findings reveal C/EBPalpha regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4(Cdt2) mediated degradation of p21. PMID: 25483090
CDK1 activity blocks CRL4CDT2 by preventing chromatin recruitment of the substrate receptor, CDT2. PMID: 25411249
while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers PMID: 24699724
CRL4(Cdt2)-dependent degradation of TDG occurs in S phase because of the requirement for TDG to interact with chromatin-loaded PCNA, and this degradation is important for preventing toxicity from excess TDG. PMID: 24962565
Data shows that phosphorylation of Cdt2 at T464 is important fot its interaction with Cdt2. PMID: 25154416
TGF-beta signaling promotes exit from the cell cycle and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2. PMID: 23892434
ubiquitination of p12 through CRL4(Cdt2) and subsequent degradation form one mechanism by which a cell responds to DNA damage to inhibit fork progression. PMID: 24022480
Data indicate that depleting ubiquitin E3 ligase CRL4(CDT2/DCAF2) mimicked the pharmacological effects of MLN4924. PMID: 23995842
Data indicate that CRL4(Cdt2) regulates the degradation of the p12 subunit of Pol delta4. PMID: 23913683
Non-canonical CRL4A/4B(CDT2) interacts with RAD18 to modulate post replication repair and cell survival. PMID: 23555860
The functional interaction between FBXO11 and CDT2 is evolutionary conserved from worms to humans and plays an important role in regulating the timing of cell-cycle exit. PMID: 23478441
Migration of epithelial cells is stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8. PMID: 23478445
ATR, activated after DNA damage, phosphorylates Cdt2 and promotes the rapid degradation of Cdt1 after UV irradiation in the G1 phase of the cell cycle. PMID: 23029527
CRL4 is a major regulator of CHK1 stability. CRL4CDT2 targets CHK1 for ubiquitination in the nucleoplasm, and for PCNA-independent degradation. CHK1 is required for G2 arrest in CDT2-depleted cells. PMID: 23109433
The turnover of SET8 is accelerated after ultraviolet irradiation dependent on the CRL4(CDT2) ubiquitin ligase and PCNA. PMID: 21220508
data identified miR-30a-5p as a tumor-suppressing miRNA in colon cancer cells exerting its function via modulation of DTL expression, which is frequently overexpressed in colorectal cancer PMID: 22287560
CDT2, a 1q-located candidate gene encoding a protein involved in ubiquitin ligase activity and significantly overexpressed in 1qG Ewing sarcoma, was validated in vitro and in vivo proving its major contribution to this molecular and clinical phenotype PMID: 21822310
Studies indicate the modular architecture of DDB1-CUL4 in complex with DDB2, CSA and CDT2 in DNA repair of UV-induced DNA lesions. PMID: 21550341
Studies suggest that DNA damage-induced ubiquitination or sumoylation of PCNA prevents CRL4Cdt2-dependent degradation by inhibiting binding of Cdt1 to PCNA. PMID: 21846465
N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) triggers MSH2 and Cdt2 protein-dependent degradation of the cell cycle and mismatch repair (MMR) inhibitor protein p21Waf1/Cip1. PMID: 21725088
Cdt1 degradation following UV irradiation occurs rapidly at damaged sites due to PCNA chromatin loading and the recruitment of Cdt1 and CRL4(Cdt2), before DNA damage repair is completed PMID: 20929861
Results demonstrate a central role of CRL4(Cdt2)-dependent cell-cycle regulation of Set8 for the maintenance of a stable epigenetic state essential for cell viability. PMID: 20932471
CRL4(Cdt2)-dependent destruction of Set8 in S phase preserves genome stability by preventing aberrant chromatin compaction during DNA synthesis. PMID: 20932472
This study identifies CRL4-Cdt2 ubiquitin ligase to promote the ubiquitin-dependent proteolysis of the histone H4 methyltransferase Set8 during S-phase of the cell cycle and after UV-irradiation in a reaction that is dependent on PCNA. PMID: 20932471
miR-215, through the suppression of DTL expression, induces a decreased cell proliferation leading to an increase in chemoresistance PMID: 20433742
PCNA, L2DTL and the DDB1-CUL4A complex play critical and differential roles in regulating the protein stability of p53 and MDM2/HDM2 in unstressed and stressed cells. PMID: 16861890
L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage. PMID: 16861906
These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication. PMID: 16949367
DTL promotes genomic stability through two distinct mechanisms. First, it is an essential component of the CUL4-DDB1 complex that controls CDT1 levels, thereby preventing rereplication. Second, it is required for the early G2/M checkpoint. PMID: 17085480
L2DTL encodes a nuclear protein with centrosome targeting in mitosis, and plays important roles in DNA synthesis, cell cycle progression, cytokinesis, proliferation, and differentiation. PMID: 17106265
roles of DTL/RAMP in growth of breast cancer cells and suggest that DTL/RAMP might be a promising molecular target for treatment of breast cancer. PMID: 18542055
CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation PMID: 18703516
RAMP plays an oncogenic role in gastric carcinogenesis PMID: 19672268
CDT2/DTL functions as a substrate recognition factor for the Cul4-DDB1-Roc1 E3 ubiquitin ligase to promote PCNA-dependent ubiquitylation and degradation of the CDK inhibitor CDKN1A, both in S-phase of the cell cycle and after UV irradiation. PMID: 18794347

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Subcellular Location

Nucleus. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Chromosome. Note=Nuclear matrix-associated protein. Translocates from the interphase nucleus to the metaphase cytoplasm during mitosis.

Protein Families

WD repeat cdt2 family

Tissue Specificity

Expressed in placenta and testis, very low expression seen in skeletal muscle. Detected in all hematopoietic tissues examined, with highest expression in thymus and bone marrow. A low level detected in the spleen and lymph node, and barely detectable leve

Database Links

HGNC: 30288

OMIM: 610617

KEGG: hsa:51514

STRING: 9606.ENSP00000355958

UniGene: Hs.656473

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Code	CSB-RA190124A0HU
Size	US$210
	Order now
Image	IHC image of CSB-RA190124A0HU diluted at 1:100 and staining in paraffin-embedded human placenta tissue performed on a Leica BondTM system. After dewaxing and hydration, antigen retrieval was mediated by high pressure in a citrate buffer (pH 6.0). Section was blocked with 10% normal goat serum 30min at RT. Then primary antibody (1% BSA) was incubated at 4°C overnight. The primary is detected by a Goat anti-rabbit polymer IgG labeled by HRP and visualized using 0.05% DAB. Immunofluorescence staining of Hela cell with CSB-RA190124A0HU at 1:50, counter-stained with DAPI. The cells were fixed in 4% formaldehyde, permeabilized using 0.2% Triton X-100 and blocked in 10% normal Goat Serum. The cells were then incubated with the antibody overnight at 4°C. The secondary antibody was Alexa Fluor 488-congugated AffiniPure Goat Anti-Rabbit IgG(H+L). Overlay Peak curve showing jurkat cells stained with CSB-RA190124A0HU (red line) at 1:100. The cells were fixed in 4% formaldehyde and permeated by 0.2% TritonX-100 for 10min. Then 10% normal goat serum to block non-specific protein-protein interactions followed by the antibody (1ug/110⁶cells) for 45min at 4℃. The secondary antibody used was FITC-conjugated goat anti-rabbit IgG (H+L) at 1/200 dilution for 35min at 4℃.Control antibody (green line) was Rabbit IgG (1ug/110⁶cells) used under the same conditions. Acquisition of >10,000 events was performed.
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DTL Recombinant Monoclonal Antibody

Product Details

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Target Background