Monday, August 26, 2013

estrogen receptor, another wild gene


 Estrogen receptor is another  "wild gene"
 (Interacts with so many other genes to hide its full effect, wild genes will eventually hit another gene or a silent mutation, enough to lead to a neoplastic process).

WIKIPIDIA TELLS

"Genomic

In the absence of hormone, estrogen receptors are largely located in the cytosol. Hormone binding to the receptor triggers a number of events starting with migration of the receptor from the cytosol into the nucleus, dimerization of the receptor, and subsequent binding of the receptor dimer to specific sequences of DNA known as hormone response elements. The DNA/receptor complex then recruits other proteins that are responsible for the transcription of downstream DNA into mRNA and finally protein that results in a change in cell function. Estrogen receptors also occur within the cell nucleus, and both estrogen receptor subtypes have a DNA-binding domain and can function as transcription factors to regulate the production of proteins.
The receptor also interacts with activator protein 1 and Sp-1 to promote transcription, via several coactivators such as PELP-1.[2]
Direct acetylation of the estrogen receptor alpha at the lysine residues in hinge region by p300 regulates transactivation and hormone sensitivity.[19]"
"
AT CRBCM, WE WOU;D LIKE TO STRESS THAT ONE OF THE MOST SIGNIFICANT EFFECT OF ESTROGEN IS ITS INDUCTION OF PROFOUND INDUCTION OF EPIGENETIC CHANGES BY A COMPLETE MAKE OVER OF PATTERNS OF METHYLATION, AND ITS CO-PARTNER, THE PATTERN OF miRNA(s), AS IF THIS HORMONE ATTACHES TO mRNA OR TO POLYMERASES.  ONE OF THE MOST AFFECTED GROUP OF GENE THE CLASS I ANTIGENS HLA-A AND B.  THIS SINGLE FACT (ESTROGEN SURGE AND SUBSEQUENT CHANGE IN METHYLATION PATTERNS  ) CONTROLS THE WORSENING OF MOST AUTOIMMUNE DISEASES IN WOMEN ENTERING AGE OF FERTILITY (LUPUS IS BAD BETWEEN 15-45 YEARS OF AGE IN WOMEN) . IT IS ALSO THE CAUSE OF ENDOMETRIAL CANCER IN UNOPPOSED ESTROGENIC EXPOSURE, AND ACTUALLY KILLS WOMEN BY MYOCARDIAL SILENT ATTACK AT MENOPAUSE!


ESTROGEN GENE :  "
Binds DNA as a homodimer. Can form a heterodimer with ESR2. Isoform 3 can probably homodimerize or heterodimerize with isoform 1 and ESR2. Interacts with FOXC2, MAP1S, SLC30A9, UBE1C and NCOA3 coactivator By similarity. Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent. Interacts with NCOA5 and NCOA6 coactivators. Interacts with NCOA7; the interaction is a ligand-inducible. Interacts with PHB2, PELP1 and UBE1C. Interacts with AKAP13. Interacts with CUEDC2. Interacts with KDM5A. Interacts with SMARD1. Interacts with HEXIM1. Interacts with PBXIP1. Interaction with MUC1 is stimulated by 7 beta-estradiol (E2) and enhances ERS1-mediated transcription. Interacts with DNTTIP2, FAM120B and UIMC1. Interacts with isoform 4 of TXNRD1. Interacts with KMT2D/MLL2. Interacts with ATAD2 and this interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interaction with SH2D4A blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes. Interacts with NR2C1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with DYX1C1. Interacts with PRMT2. Interacts with PI3KR1 or PI3KR2, SRC and PTK2/FAK1. Interacts with RBFOX2. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESE1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the interaction seems to require a self-association of N-terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3. Interacts with NRIP1 By similarity. "( UniProtKB/Swiss-Prot)

=======================A CAREFUL REVIEW OF EACH CITED GENE IS WARRANTED TO UNDERSTAND THE FULL SCOPE OF ESTROGEN INFLUENCE===============
Post a Comment