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"}

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)

THE "WEAKNESS" OF MEN HAS GOT TO BE IN THEIR ANDROGEN

One thing is certain, women seem to live longer than men...There seem to be many more widows than widowers!  If you look at statistics of elderly who live the longest, you are more likely to find women than men.  It is easy to say that men live a more stressful life and therefore die sooner, but one may also want to look into the main difference between men and women.  And the Androgen level comes quickly to mind!
Androgen and related receptors are part of "wild genes", that is their effect here involves many genes downstream.
When you look at the span of genes which interact with the Androgen gene, one is struck by the deep epigenetic distribution of their effects!
One particular interacting gene stands out:

"NCOA4 has been shown to interact with Peroxisome proliferator-activated receptor gamma^[4] and Androgen receptor.[ "(wikipedia)

The involvement of the PPAR gamma point to weakness of Antigen presentation and therefore a weakness in our defense mechanism.  This perhaps opens the door to understanding why men having sex with men still have the highest Kaposi Sarcoma burden?  I believe we are onto something here! look this up! NCOA4, a new target indeed!