A WILD GENE! THE EP 300

Every time we talk about a "wild gene", we get a reaction from our readers.  This is a good sign.  Basically, what we call wild gene is one full of interactions.  We talked about adapter genes which basically direct in one or the other direction of global Metabolism, but we also make sure that readers understand that these adapters can allow a gene to acquire proliferative potential by hooking it to another gene that routinely drives proliferation (such as the gene that pushes Antibody formation).  By all definitions, EP300 is a wild gene.

Another power to this gene is the fact that it leads to Malformation when it is missing:
"Rubinstein-Taybi syndrome.", THROUGH THE MAML1 GENE, THIS GENE IS IN COMPLICITY WITH THE NOTCH1.  And you know how we hold dearly the Notch as an important gene/pathway...

EP300 is involved in all major cancers including Acute Leukemia.  You remember that Acute AML cells have not fully completed differentiation.  EP300 is the master of differentiation and of course will be mutated or altered in bad AML.  So, in a way, it is prognostic!

" Somatic mutations in the EP300 gene have been found in a small number of solid tumors, including cancers of the colon and rectum, stomach, breast, and pancreas. Studies suggest that EP300 mutations may also play a role in the development of some prostate cancers, and could help predict whether these tumors will increase in size or spread to other parts of the body. In cancer cells, EP300 mutations prevent the gene from producing any functional protein. Without p300, cells cannot effectively restrain growth and division, which can allow cancerous tumors to form."

HOW MANY GENES INTERACT WITH EP300? YOU BE THE JUDGE!

"Interactions"

EP300 has been shown to interact with Mothers against decapentaplegic homolog 7,^[6] MAF,^[7] TSG101,^[8] Peroxisome proliferator-activated receptor alpha,^[9][10] NPAS2,^[11] PAX6,^[12] DDX5,^[13] MYBL2,^[14] Mothers against decapentaplegic homolog 1,^[15][16] Mothers against decapentaplegic homolog 2,^[17][18] Lymphoid enhancer-binding factor 1,^[19] SNIP1,^[20] TRERF1,^[21] STAT3,^[16] EID1,^[22][23] RAR-related orphan receptor alpha,^[24] ELK1,^[25] HIF1A,^[26][27] ING5,^[28] Peroxisome proliferator-activated receptor gamma,^[29][30] SS18,^[31] TCF3,^[32] Zif268,^[33] Estrogen receptor alpha,^[29][34][35] GPS2,^[36] MyoD,^[24][37] YY1,^[38][39] ING4,^[28] PROX1,^[7] CITED1,^[40] HNF1A,^[41] MEF2C,^[37] MEF2D,^[42][43] MAML1,^[44][45] Twist transcription factor,^[46] PTMA,^[47] IRF2,^[48] DTX1,^[49] Flap structure-specific endonuclease 1,^[50] Myocyte-specific enhancer factor 2A,^[51] CDX2,^[12] BRCA1,^[34][52] HNRPU,^[53] STAT6,^[54] CITED2,^{[55][56][57][58]} RELA,^[59][60] TGS1,^[61] CEBPB,^[62] Mdm2,^[63] NCOA6,^[64] NFATC2,^[65] Thyroid hormone receptor alpha,^[51] BCL3,^[66] TFAP2A,^[56] PCNA,^[67] P53^{[68][63][69][70][71]} and TAL1.^{[72]wikipedia"}

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 ....