PNRC2 is a 16 kDa coactivator that interacts with nuclear receptors through an SH3-binding motif.
PNRC2 (proline-rich nuclear receptor co-regulatory protein 2) was identified using mouse steroidogenic factor 1 (SF1) as bait in a yeast two-hybrid screening of a human mammary gland cDNA expression library. PNRC2 is an unusual coactivator in that it is the smallest coactivator identified so far, with a molecular weight of 16 kDa, and interacts with nuclear receptors using a proline-rich sequence. In yeast two-hybrid assays PNRC2 interacted with orphan receptors SF1 and estrogen receptor-related receptor alpha1 in a ligand-independent manner. PNRC2 was also found to interact with the ligand-binding domains of estrogen receptor, glucocorticoid receptor, progesterone receptor, thyroid receptor, retinoic acid receptor and retinoid X receptor in a ligand-dependent manner. A functional activation function 2 domain is required for nuclear receptors to interact with PNRC2. Using the yeast two-hybrid assay, the region amino acids 85-139 was found to be responsible for the interaction with nuclear receptors. This region contains an SH3 domain-binding motif (SEPPSPS) and an NR box-like sequence (LKTLL). A mutagenesis study has shown that the SH3 domain-binding motif is important for PNRC2 to interact with all the nuclear receptors tested. Our results reveal that PNRC2 has a structure and function similar to PNRC, a previously characterized coactivator. These two proteins represent a new type of nuclear receptor co-regulatory proteins.
Zhou
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Division of Immunology, Beckman Research Institute of the City of Hope, 1450 East Duarte Road, Duarte, CA 91010, USA.
Chen
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D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D047628:Estrogen Receptor alpha; D051717:Fushi Tarazu Transcription Factors; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D054339:Steroidogenic Factor 1; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics; D018909:src Homology Domains; D000097983:ERRalpha Estrogen-Related Receptor
D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D054339:Steroidogenic Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C515057:NR5A1 protein, human; C096395:PNRC1 protein, human; C437718:PNRC2 protein, human; C515058:steroidogenic factor 1, mouse