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Gene Review

RNF4  -  ring finger protein 4

Homo sapiens

Synonyms: E3 ubiquitin-protein ligase RNF4, Protein SNURF, RES4-26, RING finger protein 4, SLX5, ...
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Disease relevance of RNF4


High impact information on RNF4

  • These findings identify SNURF as a protein that is produced along with SmN from a bicistronic transcript; polycistronic mRNAs therefore are encoded in mammalian genomes where they may form functional operons [3].
  • Because SNURF is the only protein-coding sequence within the imprinting regulatory region in 15q11-q13, it may have provided the original selection for imprinting in this domain [3].
  • We show that both SNURF and SNRPN are translated in normal, but not PWS, human, and mouse tissues and cell lines [3].
  • Collectively, we have identified and characterized a ubiquitously expressed RING finger protein, SNURF, that may function as a bridging factor and regulate steroid receptor-dependent transcription by a mechanism different from those of previously identified coactivator or integrator proteins [4].
  • Overexpression of SNURF in cultured mammalian cells enhanced not only androgen, glucocorticoid, and progesterone receptor-dependent transactivation but also basal transcription from steroid-regulated promoters [4].

Biological context of RNF4


Anatomical context of RNF4


Associations of RNF4 with chemical compounds

  • This region in Rnf4 is also known to interact with several proteins including steroid receptors [11].
  • Mutation of critical cysteine residues in the RING finger domain abolished the RNF4 growth inhibition activity [9].
  • In mammalian two-hybrid assays in ZR-75 cells SNURF interactions were estrogen (E2)-dependent and were not observed with the antiestrogen ICI 182,780 [1].
  • SNURF mRNA expression was increased in ovaries of immature mice treated with diethylstilbestrol, an effect that was blocked by the pure antiestrogen ICI 182,780 [12].
  • In granulosa cell culture, SNURF mRNA accumulation was transiently increased by treatment with the LH agonists phorbol myristate and forskolin at 4 h after treatment and at 48 h in differentiated cells expressing markers of the preovulatory phenotype [12].

Physical interactions of RNF4


Regulatory relationships of RNF4

  • Using a luciferase reporter assay, we could demonstrate that the repressional function of TRPS1 is inhibited by RNF4 [11].

Other interactions of RNF4

  • This finding suggests that RNF4 is a negative regulator of TRPS1 activity [11].
  • PATZ attenuates the RNF4-mediated enhancement of androgen receptor-dependent transcription [13].
  • The association of PATZ with RNF4 switches the activation to repression of selected basal promoters [13].
  • ERbeta and SNURF/RNF4 were also clearly down-regulated at the protein level in testicular tumors [8].
  • The zinc finger region (ZFR) together with the hinge region of AR are sufficient for contacting SNURF [14].

Analytical, diagnostic and therapeutic context of RNF4


  1. Cooperative coactivation of estrogen receptor alpha in ZR-75 human breast cancer cells by SNURF and TATA-binding protein. Saville, B., Poukka, H., Wormke, M., Janne, O.A., Palvimo, J.J., Stoner, M., Samudio, I., Safe, S. J. Biol. Chem. (2002) [Pubmed]
  2. GC-rich elements flanking the transcription start site govern strong activation on the SNURF gene. Hirvonen, S.J., Santti, H., Jänne, O.A., Palvimo, J.J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  3. An imprinted, mammalian bicistronic transcript encodes two independent proteins. Gray, T.A., Saitoh, S., Nicholls, R.D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Identification of a novel RING finger protein as a coregulator in steroid receptor-mediated gene transcription. Moilanen, A.M., Poukka, H., Karvonen, U., Häkli, M., Jänne, O.A., Palvimo, J.J. Mol. Cell. Biol. (1998) [Pubmed]
  5. Interaction between the transcription factor SPBP and the positive cofactor RNF4. An interplay between protein binding zinc fingers. Lyngsø, C., Bouteiller, G., Damgaard, C.K., Ryom, D., Sanchez-Muñoz, S., Nørby, P.L., Bonven, B.J., Jørgensen, P. J. Biol. Chem. (2000) [Pubmed]
  6. A novel member of the BTB/POZ family, PATZ, associates with the RNF4 RING finger protein and acts as a transcriptional repressor. Fedele, M., Benvenuto, G., Pero, R., Majello, B., Battista, S., Lembo, F., Vollono, E., Day, P.M., Santoro, M., Lania, L., Bruni, C.B., Fusco, A., Chiariotti, L. J. Biol. Chem. (2000) [Pubmed]
  7. Identification and characterization of a novel RING-finger gene (RNF4) mapping at 4p16.3. Chiariotti, L., Benvenuto, G., Fedele, M., Santoro, M., Simeone, A., Fusco, A., Bruni, C.B. Genomics (1998) [Pubmed]
  8. Down-regulation of estrogen receptor beta and transcriptional coregulator SNURF/RNF4 in testicular germ cell cancer. Hirvonen-Santti, S.J., Rannikko, A., Santti, H., Savolainen, S., Nyberg, M., Jänne, O.A., Palvimo, J.J. Eur. Urol. (2003) [Pubmed]
  9. RNF4 is a growth inhibitor expressed in germ cells but not in human testicular tumors. Pero, R., Lembo, F., Di Vizio, D., Boccia, A., Chieffi, P., Fedele, M., Pierantoni, G.M., Rossi, P., Iuliano, R., Santoro, M., Viglietto, G., Bruni, C.B., Fusco, A., Chiariotti, L. Am. J. Pathol. (2001) [Pubmed]
  10. Translational regulation of a novel testis-specific RNF4 transcript. Pero, R., Lembo, F., Chieffi, P., Del Pozzo, G., Fedele, M., Fusco, A., Bruni, C.B., Chiariotti, L. Mol. Reprod. Dev. (2003) [Pubmed]
  11. The RING finger protein RNF4, a co-regulator of transcription, interacts with the TRPS1 transcription factor. Kaiser, F.J., Möröy, T., Chang, G.T., Horsthemke, B., Lüdecke, H.J. J. Biol. Chem. (2003) [Pubmed]
  12. Small nuclear RING finger protein expression during gonad development: regulation by gonadotropins and estrogen in the postnatal ovary. Hirvonen-Santti, S.J., Sriraman, V., Anttonen, M., Savolainen, S., Palvimo, J.J., Heikinheimo, M., Richards, J.S., Jänne, O.A. Endocrinology (2004) [Pubmed]
  13. PATZ attenuates the RNF4-mediated enhancement of androgen receptor-dependent transcription. Pero, R., Lembo, F., Palmieri, E.A., Vitiello, C., Fedele, M., Fusco, A., Bruni, C.B., Chiariotti, L. J. Biol. Chem. (2002) [Pubmed]
  14. Coregulator small nuclear RING finger protein (SNURF) enhances Sp1- and steroid receptor-mediated transcription by different mechanisms. Poukka, H., Aarnisalo, P., Santti, H., Jänne, O.A., Palvimo, J.J. J. Biol. Chem. (2000) [Pubmed]
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