NRIP1 regulation of apolipoprotein A1

1. A method for identifying an agent that increases expression of apolipoprotein A-1 (apoA1) comprising:

contacting a cell comprising a nucleic acid encoding the nuclear receptor-interacting protein 1 (NRIP1) protein with a candidate agent that is a DNA or RNA molecule or a combination of DNA and RNA, which is complementary to the nucleic acid sense strand, under conditions in which the nucleic acid encoding the (NRIP1) is expressed; and, if expression of NRIP1 is reduced in the presence of the candidate agent,

evaluating expression levels of apoA1 in the cell; wherein an increase in apoA1 polypeptide expression indicates that the candidate agent increases expression of apoA1.

2. The method of claim 1 wherein the candidate agent is an RNA molecule.

3. The method of claim 1 wherein the candidate agent is a DNA molecule.

4. The method of claim 1 , further comprising evaluating apoA1 production in an animal which has been administered the identified candidate agent wherein the identification of the candidate agent is confirmed if apoA1 production occurs at a higher level in the animal than in the absence of the agent.

5. The method of claim 1 wherein the NRIP1 is human NRIP1.

6. The method of claim 5 wherein the human NRIP1 comprises the amino acid sequence:

(SEQ ID NO: 4)

MLHGEELGSD VHQDSIVLLY LEGLLMHQAA GGSGLAVDKK SAGHNEEDQN FNISGSAFPL

  60

CQSNGPVLNL HLYQGSGMLH LKKARLLQSS EDWNAAKRKR LSDSIMNLNV KKEALLAGMV

 120

DSVPKGKQDS LLLASLLQSF SSRLQLVALS QQIRQSLKEQ GYALSHDSLK VEKDLRCYGV

 180

ASSHLKLLLK KSKVKDQKPD LNLPDVLKNL IRDRFAESPH HVGQSGLKVM SEPLSCAARL

 240

QAVASMVEKR ASPALSPKPS VACSQLALLL SSEAHLQOYS REHALKLQNA NQAASERLAA

 300

MARLQENGQK DVGSYQLPKG MSSHLNGQAR LSSSKLMASK SSALVFQNPM GIIPSSPKNA

 360

GYKNSLERNN IKQAANNSLL LHLLKSQLIP KPMNGHSHSE RGSIFEESSL PLLIDEYSDN

 420

NPSFLDDSSG DESSYSNCVP IDLSCKHRLE KSESDQPVSL DNFLQSLLNL WDPKVPDVDI

 480

KEDQDLSKNS KLNSHQKVLL LQLLLGHKNE ENVEKNLSPQ GVHNDVSKFN LQNYARLSVI

 540

ESPSLNRLLP VSLPPLLLSS KAGSPINLSQ HSLVIKWNSP PYVCSLQSEK LLNLASNHSM

 600

DLLKSKDPPG EKPAQNEGAQ NSALFSASKL LQNLAQCGMQ SSMSVEEQRP SKQLLLGNLD

 660

KPIGMIDRLN SPLLSNKLNA VEENKAFSSQ PLGPEPGLSG SEIENLLERR LVLQLLLGNP

 720

NKGKSEKKEK LPLRDESLQE HSERALSEQI LMVKIKSEPC DDLQIPNLNV HLSHDAKSAP

 780

FLGMAPAVQR SAPALPVSED FKSEPVSPQD FSFSKNGLLS RLLRQNQDSY LADDSDRSHR

 840

NNEMALLESK NLCMVPKKRK LYLEPLENPF KKMKNNIVDA ANNHSAPEVL YGSLLNQEEL

 900

KFSRNDLEFK YPAGHGSASE SEHRSWARES KSFNVLKQLL LSENCVRDLS PHRSNSVADS

 960

KKKGHKNNVL NSKPEFSISS LNGLMYSSLQ PSSCMDNRLF SYPGVVKLPV SPLFPEHLGC

1020

AGSRPESGLL NGCSMPSEKG PIKWVILDAE KNEYEKDSPR LLKLNPILYY MLQKGGNSVL

1080

SRELQDKDIW REASSAESVS QVLAKEELLP LAELKASFFN LRSPYNSHMG NNASRPHSAN

1140

GEVYGLLGSV LLIKKESE

1158

7. A method for identifying an agent that increases expression of apolipoprotein A-1 (apoA1) comprising contacting a sample comprising nuclear receptor-interacting protein 1 (NRIP1) and peroxisome proliferator-activated receptor (PPAR) with a candidate agent and determining if said NRIP1 and PPAR bind in the presence of the candidate agent and, if said binding is decreased, then contacting a cell expressing apoA1 with the candidate agent and determining apoA1 expression wherein said agent is identified as an agent that increases expression of apoA1 if expression of apoA1 is determined to increase in the presence of the agent.

8. The method of claim 7 for identifying an agent that increases expression of apolipoprotein A-1 (apoA1) comprising

(i) incubating a mixture comprising nuclear receptor-interacting protein 1 (NRIP1) polypeptide that is labeled with a FET donor label or FET acceptor label and peroxisome proliferator-activated receptor (PPAR) polypeptide that is labeled with the other label; under conditions which allow association between the polypeptides, in the presence of a candidate agent; wherein the donor and acceptor are chosen such that when the NRIP1 binds to PPAR, the donor and the acceptor are brought into interacting proximity, producing a detectable luminescence lifetime change in the photoluminescence lifetime of the donor; and

(ii) exposing the sample to an exciting amount of radiation, detecting the resulting emission; and calculating the apparent luminescence lifetime of the donor to quantify binding of the NRIP1 polypeptide to the PPAR; and if fluorescence by the donor occurs at a lower level than that observed in the absence of said candidate agent, then evaluating expression levels of the apoA1 in a cell in the presence of the candidate agent; wherein an increase in apoA1 polypeptide expression indicates that the candidate agent increases expression of apoA1.

9. The method of claim 7 wherein the PPAR is PPAR alpha.

10. The method of claim 7 wherein the PPAR is PPAR delta.

11. The method of claim 7 wherein the PPAR is PPAR gamma.