製品: Cyclin D1 Antibody
カタログ: DF6386
タンパク質の説明: Rabbit polyclonal antibody to Cyclin D1
アプリケーション: WB IHC IF/ICC
反応性: Human, Mouse, Rat
予測: Pig, Bovine, Dog, Chicken, Xenopus
分子量: 34kDa; 34kD(Calculated).
ユニプロット: P24385
RRID: AB_2838349

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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:500-1:2000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human,Mouse,Rat
予測:
Pig(86%), Bovine(86%), Dog(86%), Chicken(86%), Xenopus(86%)
クローナリティ:
Polyclonal
特異性:
Cyclin D1 Antibody detects endogenous levels of total Cyclin D1.
RRID:
AB_2838349
引用形式: Affinity Biosciences Cat# DF6386, RRID:AB_2838349.
コンジュゲート:
Unconjugated.
精製:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

AI327039;B cell CLL/lymphoma 1;B cell leukemia 1;B cell lymphoma 1 protein;B-cell lymphoma 1 protein;BCL 1;BCL-1;BCL-1 oncogene;BCL1;BCL1 oncogene;ccnd1;CCND1/FSTL3 fusion gene, included;CCND1/IGHG1 fusion gene, included;CCND1/IGLC1 fusion gene, included;CCND1/PTH fusion gene, included;CCND1_HUMAN;cD1;Cyl 1;D11S287E;G1/S specific cyclin D1;G1/S-specific cyclin-D1;Parathyroid adenomatosis 1;PRAD1;PRAD1 oncogene;U21B31;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
タンパク質の説明:
Activity of the cyclin-dependent kinases CDK4 and CDK6 is regulated by T-loop phosphorylation, by the abundance of their cyclin partners (the D-type cyclins), and by association with CDK inhibitors of the Cip/Kip or INK family of proteins (1). The inactive ternary complex of cyclin D/CDK4 and p27 Kip1 requires extracellular mitogenic stimuli for the release and degradation of p27 concomitant with a rise in cyclin D levels to affect progression through the restriction point and Rb-dependent entry into S-phase (2). The active complex of cyclin D/CDK4 targets the retinoblastoma protein for phosphorylation, allowing the release of E2F transcription factors that activate G1/S-phase gene expression (3). Levels of cyclin D protein drop upon withdrawal of growth factors through downregulation of protein expression and phosphorylation-dependent degradation (4). Of the three D cyclins, aberrant expression of cyclin D1 has been associated with many forms of cancer including B cell lymphomas and can directly contribute to oncogenesis by various mechanisms including gene translocation or amplification (2). Cyclin D1 also plays a critical role in mammary tissue maturation (5).
タンパク質配列:
MEHQLLCCEVETIRRAYPDANLLNDRVLRAMLKAEETCAPSVSYFKCVQKEVLPSMRKIVATWMLEVCEEQKCEEEVFPLAMNYLDRFLSLEPVKKSRLQLLGATCMFVASKMKETIPLTAEKLCIYTDNSIRPEELLQMELLLVNKLKWNLAAMTPHDFIEHFLSKMPEAEENKQIIRKHAQTFVALCATDVKFISNPPSMVAAGSVVAAVQGLNLRSPNNFLSYYRLTRFLSRVIKCDPDCLRACQEQIEALLESSLRQAQQNMDPKAAEEEEEEEEEVDLACTPTDVRDVDI

種類予測

種類予測:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
86
Bovine
86
Dog
86
Xenopus
86
Chicken
86
Zebrafish
71
Horse
0
Sheep
0
Rabbit
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P24385 基板として

Site PTM Type Enzyme
K33 Ubiquitination
K46 Methylation
K46 Ubiquitination
K50 Ubiquitination
S90 Phosphorylation P17612 (PRKACA)
K95 Ubiquitination
K96 Ubiquitination
S111 Phosphorylation
K112 Ubiquitination
K114 Ubiquitination
S131 Phosphorylation
K167 Ubiquitination
K175 Ubiquitination
K180 Ubiquitination
S197 Phosphorylation P17612 (PRKACA)
S219 Phosphorylation
Y226 Phosphorylation
S234 Phosphorylation P17612 (PRKACA)
K238 Ubiquitination
K269 Ubiquitination
T286 Phosphorylation Q13627 (DYRK1A) , Q9Y463 (DYRK1B) , P49841 (GSK3B) , O15111 (CHUK)
T288 Phosphorylation P49841 (GSK3B) , Q9Y463 (DYRK1B)

研究背景

機能:

Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.

PTMs:

Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation following DNA damage. It probably plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex.

Ubiquitinated, primarily as 'Lys-48'-linked polyubiquitination. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex containing FBXO4 and CRYAB. Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. SCF-type ubiquitination is dependent on Thr-286 phosphorylation (By similarity). Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner. Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization.

細胞の位置付け:

Nucleus. Cytoplasm. Nucleus membrane.
Note: Cyclin D-CDK4 complexes accumulate at the nuclear membrane and are then translocated to the nucleus through interaction with KIP/CIP family members.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
サブユニット構造:

Interacts with FBXO4 (By similarity). Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Component of the ternary complex CCND1/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Interacts directly with CDKN1B. Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears to occur independently of phosphorylation. Can form similar complexes with either CDKN1A or CDKN2A. Interacts with USP2. Interacts (via cyclin N-terminal domain) with INSM1 (via N-terminal region); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and inhibits CDK4 activity. Interacts with CDK4; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression.

タンパク質ファミリー:

Belongs to the cyclin family. Cyclin D subfamily.

研究領域

· Cellular Processes > Cell growth and death > Cell cycle.   (View pathway)

· Cellular Processes > Cell growth and death > p53 signaling pathway.   (View pathway)

· Cellular Processes > Cell growth and death > Cellular senescence.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Focal adhesion.   (View pathway)

· Cellular Processes > Cellular community - eukaryotes > Tight junction.   (View pathway)

· Environmental Information Processing > Signal transduction > FoxO signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > AMPK signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Wnt signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Hedgehog signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Apelin signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Hippo signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Jak-STAT signaling pathway.   (View pathway)

· Human Diseases > Drug resistance: Antineoplastic > Endocrine resistance.

· Human Diseases > Infectious diseases: Viral > Hepatitis B.

· Human Diseases > Infectious diseases: Viral > Measles.

· Human Diseases > Infectious diseases: Viral > Human papillomavirus infection.

· Human Diseases > Infectious diseases: Viral > HTLV-I infection.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Overview > Viral carcinogenesis.

· Human Diseases > Cancers: Overview > Proteoglycans in cancer.

· Human Diseases > Cancers: Overview > MicroRNAs in cancer.

· Human Diseases > Cancers: Specific types > Colorectal cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Pancreatic cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Endometrial cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Glioma.   (View pathway)

· Human Diseases > Cancers: Specific types > Prostate cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Thyroid cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Melanoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Bladder cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Chronic myeloid leukemia.   (View pathway)

· Human Diseases > Cancers: Specific types > Acute myeloid leukemia.   (View pathway)

· Human Diseases > Cancers: Specific types > Small cell lung cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Non-small cell lung cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Breast cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

· Human Diseases > Cardiovascular diseases > Viral myocarditis.

· Organismal Systems > Endocrine system > Prolactin signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Thyroid hormone signaling pathway.   (View pathway)

· Organismal Systems > Endocrine system > Oxytocin signaling pathway.

参考文献

1). GLI1 activation by non-classical pathway integrin αvβ3/ERK1/2 maintains stem cell-like phenotype of multicellular aggregates in gastric cancer peritoneal metastasis. Cell Death & Disease, 2019 (PubMed: 31366904) [IF=9.0]

Application: WB    Species: mouse    Sample: BGC823MCAs and SGC7901MCAs

Fig. S5 |a Western blottingting showing the most pronounced effect of Smo silencing in the shSmo #2 group in BGC823MCAs and SGC7901MCAs. d Western blottingting showing decreased c-Myc and Cyclin D1 in the group of Integrin αvβ3 co-simulator ligand RGD plus ERK1/2 inhibitor PD-184161 or PD-184161 alone compared to the blank control. Each bar in the figure represents the mean ± SEM of triplicates. ns, no significance; *p < 0.05,**p < 0.01.

2). α2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/β-catenin pathway. Oncogenesis, 2017 (PubMed: 28553930) [IF=6.2]

Application: WB    Species: human    Sample: Huh-7 cells

Figure 5. Upregulation of ST6Gal-I activates PI3K/Akt, and Wnt/β-catenin signaling pathways in Huh-7 cells. (a, c, e) Main protein components of the PI3K/Akt/MAPK/β-catenin signaling pathway in Huh-7 cells were measured using western blotting.

3). RECQL4 regulates DNA damage response and redox homeostasis in esophageal cancer. Cancer Biology & Medicine, 2021 (PubMed: 33628589) [IF=5.5]

Application: WB    Species: human    Sample: ESCC cells

Figure 4 |The loss of RECQL4 induces cell cycle arrest and cellular senescence. . (D) The protein levels of c-myc, p21, cyclin D, CDK6, cyclin E, Bax, and Bcl-2 were determined by Western blot in stable Tet-on inducible RECQL4 knockdown cell lines (KYSE30 and TE-1 cells) (+Dox) and controls (–Dox). Experiments were independently repeated 3 times. All data indicate the mean ±SD. *P < 0.05; **P < 0.01; ***P < 0.001.

Application: WB    Species: Human    Sample: KYSE30 and TE-1 cells

Figure 4 The loss of RECQL4 induces cell cycle arrest and cellular senescence. (A) Depletion of RECQL4 by siRNA. RECQL4 protein levels were measured by Western blot. KYSE30 and TE-1 cells were transfected with siRNA duplexes (200 nM) specific to RECQL4 or negative oligo in serum-free medium for 4 h, then replaced with complete medium for 24 h. Whole cell extracts were collected for Western blot analysis using RECQL4 antibodies. (B) Cell cycle distributions in RECQL4 knockdown cell lines (KYSE30 and TE-1 cells) and controls were determined by flow cytometry. (C) Cellular senescence was examined by SA-β-gal staining. Microscopic magnification (×200), Scale bar: 50 μm. (D) The protein levels of c-myc, p21, cyclin D, CDK6, cyclin E, Bax, and Bcl-2 were determined by Western blot in stable Tet-on inducible RECQL4 knockdown cell lines (KYSE30 and TE-1 cells) (+Dox) and controls (–Dox). Experiments were independently repeated 3 times. All data indicate the mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001.

4). A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1. CELLULAR SIGNALLING, 2020 (PubMed: 31689506) [IF=4.8]

5). ST3Gal IV Mediates the Growth and Proliferation of Cervical Cancer Cells In Vitro and In Vivo Via the Notch/p21/CDKs Pathway. Frontiers in Oncology, 2021 (PubMed: 33598419) [IF=4.7]

6). LncRNA PVT1 promotes the malignant progression of acute myeloid leukaemia via sponging miR-29 family to increase WAVE1 expression. PATHOLOGY, 2021 (PubMed: 33558065) [IF=4.5]

Application: WB    Species: Human    Sample: tumour tissues

Fig. 6 PVT1/WAVE1 axis regulates xenograft growth in vivo. (A) Photograph of the xenograft tumours from different groups. (B) Tumour volumes at the indicated time points and (C) tumour weight are presented. (D) Apoptosis in tumour tissues was evaluated by TUNEL assay. (E) Expression of Ki-67 in tumour tissues was determined by immunohistochemical staining. (F) The protein levels of Bax, Bcl-2, cleaved Caspase 3, p21, and cyclin D1 in tumour tissues was assessed by western blotting. All data are expressed as mean ± standard deviation. *p<0.05, **p<0.01, ***p<0.001 versus the indicated group.

7). Radix Actinidia chinensis Suppresses Renal Cell Carcinoma Progression: Network Pharmacology Prediction and In Vivo Experimental Validation. Analytical Cellular Pathology, 2022 (PubMed: 35942173) [IF=3.2]

Application: WB    Species: Mice    Sample: tumor tissues

Figure 6 RAC induced the apoptosis of the tumor tissue in RCC mice. (a) The apoptosis was measured by TUNEL. (b) The protein expression of Bax, Cleaved-caspase 3, Bcl-2, and Cyclin D1 was detected by western blot. ▲P < 0.05 and ▲▲P < 0.01vs. the model. Results were presented as mean ± SD. n = 3. Note: RAC: Radix Actinidia chinensis; RCC: renal cell carcinoma; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling.

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