Thymopoietin Explained

Lamina-associated polypeptide 2 (LAP2), isoforms beta/gamma is a protein that in humans is encoded by the TMPO gene.^{[1] [2]} LAP2 is an inner nuclear membrane (INM) protein.^[3]

Thymopoietin is a protein involved in the induction of CD90 in the thymus. The thymopoetin (TMPO) gene encodes three alternatively spliced mRNAs encoding proteins of 75 kDa (alpha), 51 kDa (beta) and 39 kDa (gamma) which are ubiquitously expressed in all cells. The human TMPO gene maps to chromosome band 12q22 and consists of eight exons. TMPO alpha is present diffusely expressed with the cell nucleus while TMPO beta and gamma are localized to the nuclear membrane. TMPO beta is a human homolog of the murine protein LAP2. LAP2 plays a role in the regulation of nuclear architecture by binding lamin B1 and chromosomes. This interaction is regulated by phosphorylation during mitosis. Given the nuclear localization of the three TMPO isoforms, it is unlikely that these proteins play any role in CD90 induction.

Interactions

Thymopoietin has been shown to interact with Barrier to autointegration factor 1,^[4] AKAP8L,^{[5] [6]} LMNB1^{[7] [8]} and LMNA.^{[9] [10]}

Further reading

• Harris CA, Andryuk PJ, Cline SW, Mathew S, Siekierka JJ, Goldstein G . Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2 . Genomics . 28 . 2 . 198–205 . Jul 1995 . 8530026 . 10.1006/geno.1995.1131 .
• Dechat T, Vlcek S, Foisner R . Review: lamina-associated polypeptide 2 isoforms and related proteins in cell cycle-dependent nuclear structure dynamics . Journal of Structural Biology . 129 . 2–3 . 335–45 . Apr 2000 . 10806084 . 10.1006/jsbi.2000.4212 .
• Twomey JJ, Goldstein G, Lewis VM, Bealmear PM, Good RA . Bioassay determinations of thymopoietin and thymic hormone levels in human plasma . Proceedings of the National Academy of Sciences of the United States of America . 74 . 6 . 2541–5 . Jun 1977 . 302007 . 432209 . 10.1073/pnas.74.6.2541 . 1977PNAS...74.2541T . free .
• Heavner GA, Audhya T, Goldstein G . Peptide analogs of thymopentin distinguish distinct thymopoietin receptor specificities on two human T cell lines . Regulatory Peptides . 27 . 2 . 257–62 . Feb 1990 . 2158125 . 10.1016/0167-0115(90)90044-W . 12562672 .
• Fuccello A, Audhya T, Talle MA, Goldstein G . Immunoassay for bovine serum thymopoietin: discrimination from splenin by monoclonal antibodies . Archives of Biochemistry and Biophysics . 228 . 1 . 292–8 . Jan 1984 . 6364989 . 10.1016/0003-9861(84)90070-5 .
• Hara H, Hayashi K, Ohta K, Itoh N, Ohta M . A new thymopoietin precursor gene from human thymus . Biochemistry and Molecular Biology International . 34 . 5 . 927–33 . Nov 1994 . 7703909 .
• Goldstein G, Schlesinger DH, Audhya T . Isolation and complete amino acid sequence of human thymopoietin and splenin . Proceedings of the National Academy of Sciences of the United States of America . 91 . 13 . 6249 . Jun 1994 . 8016147 . 44176 . 10.1073/pnas.91.13.6249 . 1994PNAS...91.6249G . free .
• Harris CA, Andryuk PJ, Cline SW, Mathew S, Siekierka JJ, Goldstein G . Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2 . Genomics . 28 . 2 . 198–205 . Jul 1995 . 8530026 . 10.1006/geno.1995.1131 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Berger R, Theodor L, Shoham J, Gokkel E, Brok-Simoni F, Avraham KB, Copeland NG, Jenkins NA, Rechavi G, Simon AJ . The characterization and localization of the mouse thymopoietin/lamina-associated polypeptide 2 gene and its alternatively spliced products . Genome Research . 6 . 5 . 361–70 . May 1996 . 8743987 . 10.1101/gr.6.5.361 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . Apr 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Furukawa K, Fritze CE, Gerace L . The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain . The Journal of Biological Chemistry . 273 . 7 . 4213–9 . Feb 1998 . 9461618 . 10.1074/jbc.273.7.4213 . free .
• Furukawa K, Kondo T . Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin . European Journal of Biochemistry . 251 . 3 . 729–33 . Feb 1998 . 9490046 . 10.1046/j.1432-1327.1998.2510729.x . free .
• Dechat T, Gotzmann J, Stockinger A, Harris CA, Talle MA, Siekierka JJ, Foisner R . Detergent-salt resistance of LAP2alpha in interphase nuclei and phosphorylation-dependent association with chromosomes early in nuclear assembly implies functions in nuclear structure dynamics . The EMBO Journal . 17 . 16 . 4887–902 . Aug 1998 . 9707448 . 1170818 . 10.1093/emboj/17.16.4887 .
• Furukawa K . LAP2 binding protein 1 (L2BP1/BAF) is a candidate mediator of LAP2-chromatin interaction . Journal of Cell Science . 112 (Pt 15) . 15 . 2485–92 . Aug 1999 . 10.1242/jcs.112.15.2485 . 10393804 .
• Weber PJ, Eckhard CP, Gonser S, Otto H, Folkers G, Beck-Sickinger AG . On the role of thymopoietins in cell proliferation. Immunochemical evidence for new members of the human thymopoietin family . Biological Chemistry . 380 . 6 . 653–60 . Jun 1999 . 10430029 . 10.1515/BC.1999.081 . 12957414 .
• Dechat T, Korbei B, Vaughan OA, Vlcek S, Hutchison CJ, Foisner R . Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins . Journal of Cell Science . 113 Pt 19 . 19 . 3473–84 . Oct 2000 . 10.1242/jcs.113.19.3473 . 10984438 .
• Martins SB, Eide T, Steen RL, Jahnsen T, Skålhegg BS, Collas P . HA95 is a protein of the chromatin and nuclear matrix regulating nuclear envelope dynamics . Journal of Cell Science . 113 Pt 21 . 21 . 3703–13 . Nov 2000 . 10.1242/jcs.113.21.3703 . 11034899 . free .

Notes and References

1. Harris CA, Andryuk PJ, Cline S, Chan HK, Natarajan A, Siekierka JJ, Goldstein G . Three distinct human thymopoietins are derived from alternatively spliced mRNAs . Proceedings of the National Academy of Sciences of the United States of America . 91 . 14 . 6283–7 . Jul 1994 . 7517549 . 44185 . 10.1073/pnas.91.14.6283 . 1994PNAS...91.6283H . free .
2. Web site: Entrez Gene: TMPO thymopoietin.
3. Holmer L, Worman HJ . Inner nuclear membrane proteins: functions and targeting . Cellular and Molecular Life Sciences . 58 . 12–13 . 1741–7 . Nov 2001 . 11766875 . 10.1007/PL00000813 . 20902309 .
4. Furukawa K . LAP2 binding protein 1 (L2BP1/BAF) is a candidate mediator of LAP2-chromatin interaction . Journal of Cell Science . 112 (Pt 15) . 15 . 2485–92 . Aug 1999 . 10.1242/jcs.112.15.2485 . 10393804 .
5. Martins SB, Eide T, Steen RL, Jahnsen T, Skålhegg BS, Collas P . HA95 is a protein of the chromatin and nuclear matrix regulating nuclear envelope dynamics . Journal of Cell Science . 113 Pt 21 . 21 . 3703–13 . Nov 2000 . 10.1242/jcs.113.21.3703 . 11034899 . free .
6. Martins S, Eikvar S, Furukawa K, Collas P . HA95 and LAP2 beta mediate a novel chromatin-nuclear envelope interaction implicated in initiation of DNA replication . The Journal of Cell Biology . 160 . 2 . 177–88 . Jan 2003 . 12538639 . 2172640 . 10.1083/jcb.200210026 .
7. Furukawa K, Kondo T . Identification of the lamina-associated-polypeptide-2-binding domain of B-type lamin . European Journal of Biochemistry . 251 . 3 . 729–33 . Feb 1998 . 9490046 . 10.1046/j.1432-1327.1998.2510729.x . free .
8. Foisner R, Gerace L . Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation . Cell . 73 . 7 . 1267–79 . Jul 1993 . 8324822 . 10.1016/0092-8674(93)90355-T . 10641633 .
9. Markiewicz E, Dechat T, Foisner R, Quinlan RA, Hutchison CJ . Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein . Molecular Biology of the Cell . 13 . 12 . 4401–13 . Dec 2002 . 12475961 . 138642 . 10.1091/mbc.E02-07-0450 .
10. Dechat T, Korbei B, Vaughan OA, Vlcek S, Hutchison CJ, Foisner R . Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins . Journal of Cell Science . 113 Pt 19 . 19 . 3473–84 . Oct 2000 . 10.1242/jcs.113.19.3473 . 10984438 .