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Zellzyklus

Any growing organism – regardless of it being single- or multi-cellular – rests upon the reiteration the growth and division of existing cells under favorable conditions. During each round of this process, the cell cycles through an ordered series of events in which its genetic information is duplicated and then splits up into two cells. These events are tightly regulated and certain checkpoints must be passed in order for the cell cycle to be completed. The loss of control of these processes is a hallmark of cancer.

The cell cycle is split up into four major phases based on the events unfolding in the cell. During the first gap phase (G1) the proteins are produced that are essential for DNA replication. The genetic information is then being replicated during the synthesis (S) phase. In the second gap phase (G2) all the components that are necessary for the separation of the duplicated DNA during the subsequent mitosis (M phase). Cells that are not actively dividing are considered to be in a quiescent state in the resting phase G0. Two checkpoints between G1/S and G2/M phase must be passed in order for the cell cycle to progress.

Once replication, DNA replication must be finished. Therefore, the major checkpoint in the cell cycle is the restriction (R) point between G1 and S phases, prior to DNA duplication, at which the cycle progresses depending on mitogenic or inhibitory factors such as DNA damage and signals from various signaling pathways. A second checkpoint is at the intersection between G2 and M phases. Progression from one phase to another is controlled by cyclin dependent kinases (CDK) and their activators, cyclins. Latter proteins are unstable and their cellular concentration cycles throughout the cell cycle. Accordingly, specific cyclin-CDK complexes are characteristic for the different cell cycle phases. In addition, their activity is further modulated by CDK inhibitors. Collectively, these factors maintain balance on a cellular level and beyond.

Pathway Abbildung als PDF downloaden

Cyclin Dependent Kinase

CDK1 (Cyclin-Dependent Kinase 1):

Immunohistochemical analysis of paraffin-embedded human breast carcinoma tissue using CDC2 (Ab-15) antibody (E021236).

The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity... More...

CDK2 (Cyclin-Dependent Kinase 2):

Anti-CDK2 mouse monoclonal antibody (ABIN2454724) immunofluorescent staining of COS7 cells transiently transfected by pCMV6-ENTRY CDK2 (RC200494).

The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2. It is a catalytic subunit of the cyclin-dependent protein kinase complex, whose activity is restricted to the G1-S phase, and essential for cell cycle G1/S phase transition. This protein associates with and... More...

CDK4 (Cyclin-Dependent Kinase 4):

CDK6 (Cyclin-Dependent Kinase 6):

Western blot detection of CRK in LNCAP, A431, MCF7&HT1080 cell lysates using CRK antibody (1:1000 diluted) .

CDK2AP2 (Cyclin-Dependent Kinase 2 Associated Protein 2):

CDK3 (Cyclin-Dependent Kinase 3):

CDKL3 (Cyclin-Dependent Kinase-Like 3):

CDK5 (Cyclin-Dependent Kinase 5):

CDK7 (Cyclin-Dependent Kinase 7):

CDK8 (Cyclin-Dependent Kinase 8):

CDK9 (Cyclin-Dependent Kinase 9):

Cyclins

CCNB1 - Cyclin B1

Immunohistochemistry of Human liver cancer using CCNB1 Polyclonal Antibody at dilution of 1:20

The protein encoded by this gene is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). Two alternative transcripts have been found, a constitutively expressed transcript and a cell cycle-regulated transcript, that is expressed predominantly during G2/M phase. The different transcripts result from the use of... More...

CCNE1 - Cyclin E1

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex... More...

CCNB2 - Cyclin B2

Dot blot analysis of CCNB2 Antibody (Phospho S11) Phospho-specific Pab (ABIN1881160) on nitrocellulose membrane. 50 ng of Phospho-peptide or Non Phospho-peptide per dot were adsorbed. Antibody working concentrations are 0.6 µg per mL.

CCNE2 - Cyclin E2

CCNA1 - Cyclin A1:

CCNA2 - Cyclin A:

CCNB3 - Cyclin B3:

CCNC - Cyclin C:

CCND1 - Cyclin D1:

CCND2 - Cyclin D2:

CCND3 - Cyclin D3:

CCNH - Cyclin H:

CCNI - Cyclin I:

G1-S Checkpoint

CDC25A (Cell Division Cycle 25 Homolog A (S. Pombe)):

Immunohistochemistry of Human thyroid cancer using CDC25A Polyclonal Antibody at dilution of 1:50

CDC25A is a member of the CDC25 family of phosphatases. CDC25A is required for progression from G1 to the S phase of the cell cycle. It activates the cyclin-dependent kinase CDC2 by removing two phosphate groups. CDC25A is specifically degraded in response to DNA damage, which prevents cells with chromosomal abnormalities from progressing through cell division. CDC25A is an oncogene, although... More...

CDKN2B (Cyclin-Dependent Kinase Inhibitor 2B (p15, Inhibits CDK4)):

CDKN1A (Cyclin-Dependent Kinase Inhibitor 1A (p21, Cip1)):

Immunohistochemical analysis of paraffin-embedded human breast carcinoma tissue using p21Cip1 (phospho-Thr145) antibody (E011206).

FOXO1 (Forkhead Box O1):

FOXO3 (Forkhead Box O3):

FOXO4 (Forkhead Box O4):

SMAD2 (SMAD, Mothers Against DPP Homolog 2):

SMAD3 (SMAD, Mothers Against DPP Homolog 3):

SMAD4 (SMAD Family Member 4):

BMI1 (BMI1 Polycomb Ring Finger Oncogene):

MNAT1 (Menage A Trois Homolog 1, Cyclin H Assembly Factor (Xenopus Laevis)):

CDC25B (Cell Division Cycle 25 Homolog B (S. Pombe)):

CDC25C (Cell Division Cycle 25 Homolog C (S. Pombe)):

RASGRF1 (Ras Protein-Specific Guanine Nucleotide-Releasing Factor 1):

CDKN2C (Cyclin-Dependent Kinase Inhibitor 2C (p18, Inhibits CDK4)):

CDKN2D (Cyclin-Dependent Kinase Inhibitor 2D (p19, Inhibits CDK4)):

CDKN1A (Cyclin-Dependent Kinase Inhibitor 1A (p21, Cip1)):

CDKN1B (Cyclin-Dependent Kinase Inhibitor 1B (p27, Kip1)):

CDKN1C (Cyclin-Dependent Kinase Inhibitor 1C (p57, Kip2)):

MYC - C-MYC:

E2F/RB

RB1 - Retinoblastoma 1

Western blot analysis of extract from K562 cells untreated or treated with 10% serum after 48 hours of starvation, using Rb (Ab-780) antibody (E021110, Lane 1 and 2) and Rb (phospho-Ser780) antibody (E011132, Lane 3 and 4).

The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder... More...

E2F1 (E2F Transcription Factor 1):

The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a... More...

E2F2 (E2F Transcription Factor 2):

E2F4 (E2F Transcription Factor 4, P107/p130-Binding):

TFDP1 - DP1:

TFDP2 - DP2:

RBL1 - p107:

RBL2 - p130:

G2-M Checkpoint

CHEK1 (Checkpoint Kinase 1):

CHEK2 (Checkpoint Kinase 2):

Western blot analysis of extract from HL60 cells using Chk2.

MNAT1 (Menage A Trois Homolog 1, Cyclin H Assembly Factor (Xenopus Laevis)):

CDC25A (Cell Division Cycle 25 Homolog A (S. Pombe)):

CDC25B (Cell Division Cycle 25 Homolog B (S. Pombe)):

CDC25C (Cell Division Cycle 25 Homolog C (S. Pombe)):

RASGRF1 (Ras Protein-Specific Guanine Nucleotide-Releasing Factor 1):

WEE1 (WEE1 Homolog (S. Pombe)):

MYT1 (Myelin Transcription Factor 1):

PLK1 (Polo-Like Kinase 1):

PPM1D (Protein Phosphatase, Mg2+/Mn2+ Dependent, 1D):

GADD45A (Growth Arrest and DNA-Damage-Inducible, alpha):

GADD45B (Growth Arrest and DNA-Damage-Inducible, beta):

GADD45G (Growth Arrest and DNA-Damage-Inducible, gamma):

MDM4 - MDM4-binding Protein:

BRCA1 (Breast Cancer 1):

RBBP8 - Retinoblastoma Binding Protein 8:

HIPK2 (Homeodomain Interacting Protein Kinase 2):

TOP2A - Topoisomerase II alpha:

TERF1 - TRF1:

TERF2 - TRF2:

TINF2 (TIN2):

TPP1 (Tripeptidyl Peptidase I):

POT1 (Protection of Telomeres 1 Homolog (S. Pombe)):

TERF2IP - RAP1:

AURKA - Aurora A:

CDKN1A (Cyclin-Dependent Kinase Inhibitor 1A (p21, Cip1)):

MDM2 (Mdm2, p53 E3 Ubiquitin Protein Ligase Homolog (Mouse)):

M Phase

INCENP (Inner Centromere Protein Antigens 135/155kDa):

INCENP mAb tested by immunofluorescence. Top left: HeLa cells stained with INCENP monoclonal antibody at a 1:1,000 dilution. Top right: Same cells stained with alpha Tubulin mAb. Bottom left: Same cells stained with DAPI. Bottom right: Merge of all 3 images.

In mammalian cells, 2 broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger,' or transiently interacting, proteins (reviewed by Choo, 1997). The constitutive proteins include CENPA (centromere protein A\; MIM 117139), CENPB (MIM 117140), CENPC1 (MIM 117141), and CENPD (MIM 117142). The term 'passenger proteins' encompasses... More...

AURKB - Aurora Kinase B:

AURKC - Aurora Kinase C:

CDCA8 (Cell Division Cycle Associated 8):

BIRC5 (Baculoviral IAP Repeat-Containing 5):

EPR1 (Early-Phytochrome-Responsive1):

CSN Complex

GPS1 (G Protein Pathway Suppressor 1):

WB Image Sample(30 μg of whole cell lysate) A:HeLa S3 , B:MOLT4 , 15% SDS PAGE antibody diluted at 1:1000

COPS6 (COP9 Constitutive Photomorphogenic Homolog Subunit 6 (Arabidopsis)):

Sample Type: 1. ABAE cells2. CHO-IR cellsPrimary Dilution: 1:200Secondary Anitbody: HRP conjugated anti-rabbitImage Submitted By: Dr. Elah PickUniversity of Haifa at Oranim

COPS2 - COP9 Constitutive Photomorphogenic Homolog Subunit 2 (Arabidopsis):

COPS2 Proteine

COPS3 (COP9 Constitutive Photomorphogenic Homolog Subunit 3 (Arabidopsis)):

COPS4 (COP9 Constitutive Photomorphogenic Homolog Subunit 4 (Arabidopsis)):

COPS5 (COP9 Constitutive Photomorphogenic Homolog Subunit 5 (Arabidopsis)):

COPS7A (COP9 Constitutive Photomorphogenic Homolog Subunit 7A (Arabidopsis)):

COPS7B (COP9 Constitutive Photomorphogenic Homolog Subunit 7B (Arabidopsis)):

COPS8 (COP9 Constitutive Photomorphogenic Homolog Subunit 8 (Arabidopsis)):

SCF Complex

CUL1 - Cullin 1

Western blot analysis of extracts of various cell lines, using CUL1 antibody.

Core component of multiple cullin-RING-based SCF (SKP1- CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the... More...

SKP1 (S-Phase Kinase-Associated Protein 1):

RBX1 (Ring-Box 1, E3 Ubiquitin Protein Ligase):

BTRC (beta-Transducin Repeat Containing):

DREAM complex

RBL1 - p107

Anti-p107 antibody, IHC(P) IHC(P): Rat Intestine Tissue

RBL2 - p130

Immunohistochemical staining of mouse tissue using anti-pRb2/p130 antiserum. The staining shows the location of pRb2/p130 in developing mouse tissue. Other detection systems should yield similar results. Sections were cut at 5-7 um, mounted on glass and dried overnight at 37°C. All sections were deparaffinized in Xylene, rehydrated through a graded alcohol series and washed in phosphatebuffered saline (PBS). PBS was used for all subsequent washes and for antiserum dilution. Tissue sections were quenched sequentially in 0.5% hydrogen peroxide and blocked with diluted 10% normal goat anti-rabbit serum. Slides were incubated at 20° C for 1 h with rabbit anti-pRb2/p130 (1:500) dilution, washed, and then reacted with diluted goat anti-rabbit biotinylated antibody for 30 min. Slides were then reacted with streptavidin-peroxidase conjugate for 30 min at 20°C. Diaminobenzidine was used as the final chromogen. Negative controls for each tissue section were prepared by substituting the primary antiserum with pre-immune serum.

E2F4 (E2F Transcription Factor 4, P107/p130-Binding):

TFDP1 - DP1

Western blot analysis of Hela, HUVEC and HepG2 cells , using TFDP1 Polyclonal Antibody at dilution of 1:500