One of the main activities of cancer cells to complete their "criminal enterprise" is to escape proliferation control, and cancer cells have known this and have mastered the way to achieve this very efficiently through the Cadherins. Though it is emphasized that the cancer cells reduce E-cadherin expression to free themselves from their neighbors by reducing Adhesion molecules, the truth is that there is a more ominous enterprise going on. Degradation of E-cadherin through Ubiquitilation consumes or distracts E3 from its main job which is to remove some of the Inhibitors to CDK, LEAVING THE CELL WITH UNCHECKED CELL DIVISION.
Occupying the HAKAI (ASSASSIN) would be helpful in achieving control of the process.
The E3 ubiquitin-protein ligase Hakai (HAKAI) also known as Casitas B-lineage lymphoma-transforming sequence-like protein 1 (CBLL1) is an enzyme that in humans is encoded by the CBLL1 gene.[1] This gene encodes an E3 ubiquitin ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation.
Showing posts with label CDK. Show all posts
Showing posts with label CDK. Show all posts
Sunday, November 3, 2013
Saturday, November 2, 2013
Critical importance of the Notch1
TSG1, HGS, and STAM2 appear critical in the importance of the NOTCH1.
We have stressed the importance of the NOTCH in cancer and wanted to provide some of the proof for the supportive evidence found in the literature. The Notch through its interaction with MAML1, easily affects EP300 leading to activation of TSG, a critical gene in the action of P53. Indeed P53 acts by activating TSG which leads to an increasing inhibitory activity of p21 on CDKs, blocking as a result cell division and therefore proliferation.
Inhibition at the NOTCH will therefore remove breaks to cell division and will mark a significant tendency to cancer incurability!
And I wish things stop there, but they don't:
The Activation of TSG will disturb the resting HSG which bothers the Merlin and blocks NF2 leading to the loss of growth control by contact of surrounding cells, the cell losing control of its growth...Hyperplasia can easily ensue!
The HSG now excited, engages the STAM2 and 3 things:
1. Interaction with JAK1 leading to metastasis
" Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body (wikipedia)"
the involvement of JAK-1 multiply the worsening of the situation because it will excite: PTPN11
" PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation."
and with the ELP gene, the process will affect the SMAD3 leading to loss of control of proliferation and normal ubiquitylation of inhibitory proteins.
2.S TAM2 will engage Cytokin Receptors (Cullins)
3. STAM2 will engage the tract to E3.
But the engagement of the Notch does still not stop there...
the GSK3B comes into play! and ....
We have stressed the importance of the NOTCH in cancer and wanted to provide some of the proof for the supportive evidence found in the literature. The Notch through its interaction with MAML1, easily affects EP300 leading to activation of TSG, a critical gene in the action of P53. Indeed P53 acts by activating TSG which leads to an increasing inhibitory activity of p21 on CDKs, blocking as a result cell division and therefore proliferation.
Inhibition at the NOTCH will therefore remove breaks to cell division and will mark a significant tendency to cancer incurability!
And I wish things stop there, but they don't:
The Activation of TSG will disturb the resting HSG which bothers the Merlin and blocks NF2 leading to the loss of growth control by contact of surrounding cells, the cell losing control of its growth...Hyperplasia can easily ensue!
The HSG now excited, engages the STAM2 and 3 things:
1. Interaction with JAK1 leading to metastasis
" Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body (wikipedia)"
the involvement of JAK-1 multiply the worsening of the situation because it will excite: PTPN11
" PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation."
and with the ELP gene, the process will affect the SMAD3 leading to loss of control of proliferation and normal ubiquitylation of inhibitory proteins.
2.S TAM2 will engage Cytokin Receptors (Cullins)
3. STAM2 will engage the tract to E3.
But the engagement of the Notch does still not stop there...
the GSK3B comes into play! and ....
Thursday, August 22, 2013
Processes of cancerization
One of the most intriguing steps in the neoplastic transformation is determining the actual event that led to its occurrence. We all have the perception that because of what we ingest unfortunately on a continuous basis (medications or foods we like - man clings to habits) something will get either amplified or suppressed. Certain amplifications can be deleterious or beneficial depending of where they occur or what gene is involved. It is apparent that involvement of "wild genes" (those with multiple interactions with others, including genes involved in shaping the body) are more likely to lead to malignant transformation (ie. the Androgen gene, FYN,Grb2, MTIF, etc). Secondly, knocking out break to proliferation (P53, Rb1, PTEN, and the many CDK) seems also to be a prelude to a neoplastic transformation. Alteration in "switch" genes (SOS) and molecules intermediary to various cellular/membrane events can also trigger a persistent stimulation or suppression that could affect cellular processes enough to upset a balance. Chronic hypoxia has emerged to be a potent neoplastic process inducer....(to be continued)
Friday, April 5, 2013
STRATIFIN (IN OVARIAN CANCER)
LAM et al.
" Stratifin, also known as 14-3-3 sigma protein, stimulates matrix metalloproteinase (MMP)-1 expression in dermal fibroblasts. Treatment of dermal fibroblasts with stratifin resulted in rapid and transient upregulation of c-jun and c-fos mRNA levels. Stratifin was demonstrated to increase MMP-1 protein levels. Microarray analysis of stratifin-treated fibroblasts shows an increase in Elk4/Sap1 mRNA expression and this finding was confirmed by northern blot analysis. Our results indicate that stratifin markedly increase Elk4/Sap1 mRNA expression in a time-dependent fashion. In conclusion, stratifin stimulates fibroblast MMP-1 levels through the activation of c-fos and MAPK pathway."
Our interpretation is that stratifin is part of an intergrin, its release in the Cytoplasm indeed stimulate MAPK C-JUN and c-fos. This means it is interpretated by the cell as a chemical stressor. The NF-kB is not far away. One of the most important hidden information here is the note by the authors that there is an increase of ELK4/Sap1.
ELK4 has been shown to interact with Serum response factor[4][5] and BRCA1.[6]
Serum response factor has been shown to interact with NFYA,[10] Src,[11] CREB-binding protein,[12] GTF2I,[13][14] ATF6,[15] Nuclear receptor co-repressor 2,[16] CEBPB,[17][18] GATA4,[19][20] Myogenin,[21][22] GTF2F1,[23][24] TEAD1,[25] ELK4,[15][26] Promyelocytic leukemia protein[12] and ASCC3.[27]
(wikipedia)
(PLEASE, WHEN A MOLECULE INTERACT WITH THIS MANY MOLECULE, IT IS A PERFECT, LEGITIMATE TARGET FOR THERAPY, AND SFR DOES)
ELK4 therefore control BRCA1 and serum response factor which control NFYA. This uncover what the cancer cell has to do to start the neoplastic process. It has to derail genetic repair by abrogating the action of BRAC1, but it also has to take controles of CBF complexes and NFYA and ZHXY. Remember CBF complexes control the direction of the metabolism, In essence, when it comes to function in the cell, the role of Core Binding Factors (CBF) is indistinguishable from that of TRANSCRIPTION FACTORS. They all impose the direction that the cell metabolism should take.
Remember also that because the Stratifin engages the MAPK mostly through the certain well selected CDK, it will tend to stop cell division. In Breast cancer, Stratifin is one of the earliest methylated gene slated for silencing.
CDO1:
Cysteine dioxygenase type I, IS A GENE CONTROLLING CYSTEIN METABOLISM. DEEP ANALYSIS BRINGS THIS GENE TO ELECTRON EXCHANGE FOR THE FORMATION OF CYTOCHROME C, THE WAY TO APOPTOSIS. THE CANCER CELL QUICKLY METHYLATES THIS GENE EARLY AND MUTATION HAS BEEN LINKED TO PROGNOSIS
(WORK FROM CORNELL UNIVERSITY)
" Stratifin, also known as 14-3-3 sigma protein, stimulates matrix metalloproteinase (MMP)-1 expression in dermal fibroblasts. Treatment of dermal fibroblasts with stratifin resulted in rapid and transient upregulation of c-jun and c-fos mRNA levels. Stratifin was demonstrated to increase MMP-1 protein levels. Microarray analysis of stratifin-treated fibroblasts shows an increase in Elk4/Sap1 mRNA expression and this finding was confirmed by northern blot analysis. Our results indicate that stratifin markedly increase Elk4/Sap1 mRNA expression in a time-dependent fashion. In conclusion, stratifin stimulates fibroblast MMP-1 levels through the activation of c-fos and MAPK pathway."
Our interpretation is that stratifin is part of an intergrin, its release in the Cytoplasm indeed stimulate MAPK C-JUN and c-fos. This means it is interpretated by the cell as a chemical stressor. The NF-kB is not far away. One of the most important hidden information here is the note by the authors that there is an increase of ELK4/Sap1.
ELK4 has been shown to interact with Serum response factor[4][5] and BRCA1.[6]
Serum response factor has been shown to interact with NFYA,[10] Src,[11] CREB-binding protein,[12] GTF2I,[13][14] ATF6,[15] Nuclear receptor co-repressor 2,[16] CEBPB,[17][18] GATA4,[19][20] Myogenin,[21][22] GTF2F1,[23][24] TEAD1,[25] ELK4,[15][26] Promyelocytic leukemia protein[12] and ASCC3.[27]
(PLEASE, WHEN A MOLECULE INTERACT WITH THIS MANY MOLECULE, IT IS A PERFECT, LEGITIMATE TARGET FOR THERAPY, AND SFR DOES)
ELK4 therefore control BRCA1 and serum response factor which control NFYA. This uncover what the cancer cell has to do to start the neoplastic process. It has to derail genetic repair by abrogating the action of BRAC1, but it also has to take controles of CBF complexes and NFYA and ZHXY. Remember CBF complexes control the direction of the metabolism, In essence, when it comes to function in the cell, the role of Core Binding Factors (CBF) is indistinguishable from that of TRANSCRIPTION FACTORS. They all impose the direction that the cell metabolism should take.
Remember also that because the Stratifin engages the MAPK mostly through the certain well selected CDK, it will tend to stop cell division. In Breast cancer, Stratifin is one of the earliest methylated gene slated for silencing.
CDO1:
Cysteine dioxygenase type I, IS A GENE CONTROLLING CYSTEIN METABOLISM. DEEP ANALYSIS BRINGS THIS GENE TO ELECTRON EXCHANGE FOR THE FORMATION OF CYTOCHROME C, THE WAY TO APOPTOSIS. THE CANCER CELL QUICKLY METHYLATES THIS GENE EARLY AND MUTATION HAS BEEN LINKED TO PROGNOSIS
(WORK FROM CORNELL UNIVERSITY)
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