PAX5 explained

Paired box protein Pax-5 is a protein that in humans is encoded by the PAX5 gene.^{[1] [2] [3]}

Function

The PAX5 gene is a member of the paired box (PAX) family of transcription factors. The central feature of this gene family is a novel, highly conserved DNA-binding domain, known as the paired box. The PAX proteins are important regulators in early development, and alterations in the expression of their genes are thought to contribute to neoplastic transformation. The PAX5 gene encodes the B-cell lineage specific activator protein (BSAP) that is expressed at early, but not late stages of B-cell differentiation. Its expression has also been detected in developing CNS and testis, therefore, PAX5 gene product may not only play an important role in B-cell differentiation, but also in neural development and spermatogenesis.^[3]

Clinical significance

The PAX5 gene is located in chromosome 9p13 region, which is involved in t(9;14)(p13;q32) translocations recurring in small lymphocytic lymphomas of the plasmacytoid subtype, and in derived large-cell lymphomas. This translocation brings the potent E-mu enhancer of the IgH gene locus into close proximity of the PAX5 promoters, suggesting that the deregulation of PAX5 gene transcription contributes to the pathogenesis of these lymphomas.^[3]

Up to 97% of the Reed–Sternberg cells of Hodgkin's lymphoma express Pax-5.^[4]

Interactions

PAX5 has been shown to interact with TLE4^{[5] [6]} and Death associated protein 6.^[7]

See also

• Pax genes

Further reading

• Book: Hagman J, Wheat W, Fitzsimmons D, Hodsdon W, Negri J, Dizon F . Pax-5/BSAP: Regulator of Specific Gene Expression and Differentiation in B Lymphocytes . Current Topics in Microbiology and Immunology . Signal Transduction and the Coordination of B Lymphocyte Development and Function I . 245 . 1 . 169–94 . 1999 . 10533313 . 10.1007/978-3-642-57066-7_5. 978-3-642-63017-0 .
• Calame KL, Lin KI, Tunyaplin C . Regulatory mechanisms that determine the development and function of plasma cells . Annual Review of Immunology . 21 . 205–30 . 2003 . 12524387 . 10.1146/annurev.immunol.21.120601.141138 .
• Carotta S, Holmes ML, Pridans C, Nutt SL . Pax5 maintains cellular identity by repressing gene expression throughout B cell differentiation . Cell Cycle . 5 . 21 . 2452–6 . Nov 2006 . 17102626 . 10.4161/cc.5.21.3396 . free . 20.500.11820/32181dc9-83a3-496f-be53-c380d717da39 . free .
• Stapleton P, Weith A, Urbánek P, Kozmik Z, Busslinger M . Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9 . Nature Genetics . 3 . 4 . 292–8 . Apr 1993 . 7981748 . 10.1038/ng0493-292 . 21338655 .
• Busslinger M, Klix N, Pfeffer P, Graninger PG, Kozmik Z . Deregulation of PAX-5 by translocation of the Emu enhancer of the IgH locus adjacent to two alternative PAX-5 promoters in a diffuse large-cell lymphoma . Proceedings of the National Academy of Sciences of the United States of America . 93 . 12 . 6129–34 . Jun 1996 . 8650231 . 39201 . 10.1073/pnas.93.12.6129 . 1996PNAS...93.6129B . free .
• Iida S, Rao PH, Nallasivam P, Hibshoosh H, Butler M, Louie DC, Dyomin V, Ohno H, Chaganti RS, Dalla-Favera R . The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene . Blood . 88 . 11 . 4110–7 . Dec 1996 . 8943844 . 10.1182/blood.V88.11.4110.4110. free .
• Kaneko H, Ariyasu T, Inoue R, Fukao T, Kasahara K, Teramoto T, Matsui E, Hayakawa S, Kondo N . Expression of Pax5 gene in human haematopoietic cells and tissues: comparison with immunodeficient donors . Clinical and Experimental Immunology . 111 . 2 . 339–44 . Feb 1998 . 9486401 . 1904901 . 10.1046/j.1365-2249.1998.00509.x .
• Verkoczy LK, Berinstein NL . Isolation of genes negatively or positively co-expressed with human recombination activating gene 1 (RAG1) by differential display PCR (DD RT-PCR) . Nucleic Acids Research . 26 . 19 . 4497–507 . Oct 1998 . 9742255 . 147860 . 10.1093/nar/26.19.4497 .
• Wheat W, Fitzsimmons D, Lennox H, Krautkramer SR, Gentile LN, McIntosh LP, Hagman J . The highly conserved beta-hairpin of the paired DNA-binding domain is required for assembly of Pax-Ets ternary complexes . Molecular and Cellular Biology . 19 . 3 . 2231–41 . Mar 1999 . 10022910 . 84016 . 10.1128/mcb.19.3.2231.
• Eberhard D, Busslinger M . The partial homeodomain of the transcription factor Pax-5 (BSAP) is an interaction motif for the retinoblastoma and TATA-binding proteins . Cancer Research . 59 . 7 Suppl . 1716s–1724s; discussion 1724s–1725s . Apr 1999 . 10197586 .
• Libermann TA, Pan Z, Akbarali Y, Hetherington CJ, Boltax J, Yergeau DA, Zhang DE . AML1 (CBFalpha2) cooperates with B cell-specific activating protein (BSAP/PAX5) in activation of the B cell-specific BLK gene promoter . The Journal of Biological Chemistry . 274 . 35 . 24671–6 . Aug 1999 . 10455134 . 10.1074/jbc.274.35.24671 . free .
• Nutt SL, Heavey B, Rolink AG, Busslinger M . Commitment to the B-lymphoid lineage depends on the transcription factor Pax5 . Nature . 401 . 6753 . 556–62 . Oct 1999 . 10524622 . 10.1038/44076 . 1999Natur.401..556N . 4414876 .
• Rolink AG, Nutt SL, Melchers F, Busslinger M . Long-term in vivo reconstitution of T-cell development by Pax5-deficient B-cell progenitors . Nature . 401 . 6753 . 603–6 . Oct 1999 . 10524629 . 10.1038/44164 . 1999Natur.401..603R . 12257992 .
• Kovac CR, Emelyanov A, Singh M, Ashouian N, Birshtein BK . BSAP (Pax5)-importin alpha 1 (Rch1) interaction identifies a nuclear localization sequence . The Journal of Biological Chemistry . 275 . 22 . 16752–7 . Jun 2000 . 10748034 . 10.1074/jbc.M001551200 . free .
• Eberhard D, Jiménez G, Heavey B, Busslinger M . Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family . The EMBO Journal . 19 . 10 . 2292–303 . May 2000 . 10811620 . 384353 . 10.1093/emboj/19.10.2292 .
• Roberts EC, Deed RW, Inoue T, Norton JD, Sharrocks AD . Id helix-loop-helix proteins antagonize pax transcription factor activity by inhibiting DNA binding . Molecular and Cellular Biology . 21 . 2 . 524–33 . Jan 2001 . 11134340 . 86614 . 10.1128/MCB.21.2.524-533.2001 .
• Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Küppers R, Dalla-Favera R . Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas . Nature . 412 . 6844 . 341–6 . Jul 2001 . 11460166 . 10.1038/35085588 . 2001Natur.412..341P . 4373198 .

Notes and References

1. Adams B, Dörfler P, Aguzzi A, Kozmik Z, Urbánek P, Maurer-Fogy I, Busslinger M . Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis . Genes & Development . 6 . 9 . 1589–607 . Sep 1992 . 1516825 . 10.1101/gad.6.9.1589 . free .
2. Pilz AJ, Povey S, Gruss P, Abbott CM . Mapping of the human homologs of the murine paired-box-containing genes . Mammalian Genome . 4 . 2 . 78–82 . March 1993 . 8431641 . 10.1007/BF00290430 . 30845070 .
3. Web site: Entrez Gene: PAX5 paired box gene 5 (B-cell lineage specific activator).
4. Torlakovic E, Torlakovic G, Nguyen PL, Brunning RD, Delabie J . The value of anti-pax-5 immunostaining in routinely fixed and paraffin-embedded sections: a novel pan pre-B and B-cell marker . The American Journal of Surgical Pathology . 26 . 10 . 1343–50 . Oct 2002 . 10.1097/00000478-200210000-00011 . 12360049 . 7703197 .
5. Eberhard D, Jiménez G, Heavey B, Busslinger M . Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family . The EMBO Journal . 19 . 10 . 2292–303 . May 2000 . 10811620 . 384353 . 10.1093/emboj/19.10.2292 .
6. Milili M, Gauthier L, Veran J, Mattei MG, Schiff C . A new Groucho TLE4 protein may regulate the repressive activity of Pax5 in human B lymphocytes . Immunology . 106 . 4 . 447–55 . Aug 2002 . 12153506 . 1782747 . 10.1046/j.1365-2567.2002.01456.x .
7. Emelyanov AV, Kovac CR, Sepulveda MA, Birshtein BK . The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells . The Journal of Biological Chemistry . 277 . 13 . 11156–64 . Mar 2002 . 11799127 . 10.1074/jbc.M111763200 . free .