Wednesday, June 26, 2013

1.ABCC1 GENE (WIKIPEDIA)
Multidrug resistance-associated protein 1 is a protein that in humans is encoded by the ABCC1 gene.[1][2]
The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra-and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutathione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternative splicing by exon deletion results in several splice variants but maintains the original open reading frame in all forms.[3]

=====================================================ATP IS REQUIRED FOR THE FUNCTION OF ION CHANNELS BUT THE PRIMARY DYSFUNCTION APPEARS TO INVOLVE CYTOKINES AND GROWTH FACTOR.  ITS EXISTENCE SEEMS TO CONFER RESISTANCE TO DRUGS.
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 ALSO READ 
  1. study found a cytomegalovirus UL138-mediated loss of cell surface MRP1 and reduction of substrate export by MRP1; cytomegalovirus latency-associated loss of MRP1 and accumulation of vincristine, an MRP1 substrate, depleted virus from naturally latent progenitors all of which are in vivo sites of latency
  2. This is the first study showing significant associations of a higher MRP1 protein expression with less accelerated FEV1 decline in COPD patients using long-term therapy with inhaled corticosteroids
  3. Expression of ABCC1 by HRS cells in CHL patients predicts a higher risk of treatment failure and is marginally associated with poorer failure-free survival using standard frontline chemotherapy regimens.
  4. A review of recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance, disease susceptibility and severity, and prognosis prediction.
  5. collagen/beta1 integrin/ERK signaling up-regulates the expression and function of ABCC1
  6. Substitution of two of these residues with alternative amino acids has allowed us to produce an almost cysless form of DeltaMRP1 that traffics to the plasma membrane
  7. CK2alpha and MRP1 interact physically, and recombinant CK2 phosphorylates MRP1-derived peptide in vitro in a Thr249-dependent manner.
  8. ABCB1 expression is limited to endothelial cells, whereas ABCC1 expression could mark a minority of tumor cells approaching a stem-like status.
  9. ABCB1 and ABCC1 expression correlates with different prognostic factors in pediatric patients with acute leukemia.
  10. We have demonstrated that vincristine resistance mediated by CD40 activation was induced by an increased expression of MRP1 by AKT signaling in human multiple myeloma cell lines.


2

The myeloid transcription factor GATA-2 regulates the viral UL144 gene during human cytomegalovirus latency in an isolate-specific manner.

Poole E



============================================================IS GATA 2 A VIABLE TARGET TO REDUCE DRUG RESISTANCE AND SURVIVAL OF MYELOID LEUKEMIA.
ARE LUNA AND MIEP INDICATIONS OF ROLE OF AZACITIDINE!

3.

A novel selective LSD1/KDM1A inhibitor epigenetically blocks herpes simplex virus lytic replication and reactivation from latency.

Liang Y, Quenelle D,

4.SPINK GENE

INVOLVED IN CELIAC DISEASE
WIKI"The structure of the Kazal repeat includes a large quantity of extended chain, 2 short alpha-helices and a 3-stranded anti-parallel beta sheet.[2] The inhibitor makes 11 contacts with its enzyme substrate: unusually, 8 of these important residues are hypervariable.[3] Altering the enzyme-contact residues, and especially that of the active site bond, affects the strength of inhibition and specificity of the inhibitor for particular serine proteases.[3][4] The presence of this Pfam domain is usually indicative of serine protease inhibitors, however, Kazal-like domains are also seen in the extracellular part of agrins which are not known to be proteinase inhibitors.

Kazal_2

This domain is usually indicative of serine protease inhibitors that belong to Merops inhibitor families: I1, I2, I17 and I31. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays and have a central alpha-helix, a short two-stranded antiparallel beta-sheet and several disulphide bonds.[5][6][7] The amino terminal segment of this domain binds to the active site of its target proteases, thus inhibiting their function."

WITH THEM A SLEW OF GENES COME TO YOUR ATTENTION:
Human genes encoding proteins containing Kazal-type domains include:

Kazal_1

Kazal_2




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