Showing posts with label SMAD3. Show all posts
Showing posts with label SMAD3. Show all posts

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 ....



Sunday, March 3, 2013

Smooth Muscle Myosin & Leukemia

1.SMMHC, a Smooth Muscle Myosin related marker of differentiation, but also implying the use of multiple regulatory genes that ultimately depress P53 as a way to decrease repair of DNA and allow leukemia to proceed with proliferation. this marker is  seen in Inv-16 Leukemia.  Through interaction with SMAD3, it affects TGF driven migration of leukemic cells.  It also interfere with ACTA 2, TGFBR-2 AND FBN-1,
THIS SUGGEST THAT BLOCKING MIGRATION AND IMMUNE BETA-2 RECEPTOR OF TGF COULD ADD TO ACUTE EOSINOPHILIC LEUKEMIA.  BLOCKING NUCLEAR INTERNALIZATION OF THE BETA SUBUNIT OF THE CBF WOULD HELP IN THE CBF DRIVEN LEUKEMIA IN GENERAL.


2.HOXD3
" Mutations in this particular gene cause synpolydactyly and Brachydactyly. The product of the mouse Hoxd13 gene plays a role in axial skeleton development ...
remember the role of Anti-VEGF /MEK in people with gene that impairs morphogenesis.  leukemia with this mutation could a get a trial!

3 MEIS, a cofactor to the "soul of AML" E3
remember we discussed the AML is characterized by suppression of NF-kB
that suppression is achieved by this MEIS over-expression.  it is the over expression to 
HOS protein which is
 'The homologue of Slimb (HOS) F-box protein is a receptor of the Skp1-Cullin1-F-box protein (SCF(HOS)) E3 ubiquitin ligase, which mediates ubiquitination and degradation of beta-catenin and the inhibitor of NFkappaB, IkappaB.''

Stability of homologue of Slimb F-box protein is regulated by availability of its substrate.


 You block this stuff, you release NF-kB, you slow down leukemia or at least decrease co-existing infection rates (role in transplant patients).