IMPORTANT GENE FUNCTIONS WE WILL REVISIT AND CONFIRM

1. c-MYC  increases or cause progression into S-phase and DNA replication
therefore its amplification worsen proliferation and is and prognosis factor in cancer where it is involved.
But it also means you know what you get when you block this if you can.

2. Rb1 "sequester" E2F and blocks it from causing dimerization that pushes cell into S phase, the global effect of Rb1 by hiding E2F is to block the cell in G1.
amplification of E2F1 activates CPP32  and may lead to Apoptosis.
E2F5 belong to the Dream Multicomplex structure reminiscent of CBF
Rb1 is a definite member of the Crazy Genes, it interacts with many genes including the BRCA and the Androgen Receptor gene!

This stuff act directly at Histone level and its DNA.  If you want o know gene silencing here we go:


"  leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex By similarity. In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. Ref.37"  (Uniprot.org)

"In addition to bladder cancer, somatic mutations in the RB1 gene are associated with many other types of cancer. For example, changes in the RB1 gene have been reported in some cases of lung cancer, breast cancer, a bone cancer known as osteosarcoma, and an aggressive form of skin cancer called melanoma. Somatic RB1 mutations have also been identified in some leukemias, which are cancers of blood-forming cells. Somatic RB1 mutations in cancer cells inactivate pRB so it can no longer regulate cell division effectively."(nih.gov)
question: What would happen if you target Calcineurin
Any time you act on the Histone, their remodeling, and RNA, you can affect tough cancers including Leukemias/sarcoma.

3.p16 inhibit CDK4 associated to Cyclin D1 (cell division)

 p16 has a trancript,  "this transcript contains an alternate open reading frame (ARF) that specifies a protein that is structurally unrelated to the products of the other variants. The ARF product functions as a stabilizer of the tumor suppressor protein p53, as it can interact with and sequester MDM2, a protein responsible for the degradation of p53.[4" wikipedia
This stuff Mutated in Melanoma and Pancreatic cancer....

"Concentrations of p16INK4a increase dramatically as tissue ages. Therefore p16INK4a could potentially be used as a blood test that measures how fast the body's tissues are aging at a molecular level.^{[12]"  would it explain why Pancreatic cancer is seen more in elderly?  Can we assume this mutation in elderly with pancreatic cancer?}

4. P53 acts through p21WAF1

" The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2 or -CDK1 complexes, and thus functions as a regulator of cell cycle progression at G₁."
" p53 activates numerous microRNAs (like miR-302a, miR-302b, miR-302c, and miR-302d) that directly inhibit the p21 expression"Wikipedia
Gives us a number of targets in sarcoma where P 53 is over active

5.p14 inhibit MDM2 and free P53 to act

" p14ARF is an alternate reading frame (ARF) product of the CDKN2A locus. Both p16INK4a and p14ARF are involved in cell cycle regulation. p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote transcription of genes that would carry the cell through the G₁/S checkpoint of the cell cycle. Loss of p14ARF by a homozygous mutation in the CDKN2A (INK4A) gene will lead to elevated levels in mdm2 and, therefore, loss of p53 function and cell cycle control."

LET'S GO OUT THERE FIND SARCOMA WHERE p53 IS ACTIVATED, WE KNOW WHAT TO DO NOW!