TP53BP1

Tumor protein p53 binding protein 1
PDB rendering based on 1gzh.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1GZH​, 1KZY​, 1XNI​, 2G3R​, 2IG0​, 2LVM​, 2MWO​, 2MWP​, 3LGF​, 3LGL​, 3LH0​, 4CRI​, 4RG2​, 4X34​
Identifiers
Symbols	TP53BP1 ; 53BP1; p202; p53BP1
External IDs	OMIM: 605230 MGI: 1351320 HomoloGene: 4137 GeneCards: TP53BP1 Gene
Gene ontology Molecular function • RNA polymerase II activating transcription factor binding • RNA polymerase II transcription cofactor activity • p53 binding • damaged DNA binding • protein binding • methylated histone binding • telomeric DNA binding Cellular component • condensed chromosome kinetochore • chromosome, telomeric region • nuclear chromosome, telomeric region • nucleus • nucleoplasm • replication fork • cytoplasm Biological process • DNA damage checkpoint • double-strand break repair via homologous recombination • DNA repair • double-strand break repair • transcription, DNA-templated • cellular response to DNA damage stimulus • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • positive regulation of sequence-specific DNA binding transcription factor activity • cellular response to X-ray Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7158	27223
Ensembl	ENSG00000067369	ENSMUSG00000043909
UniProt	Q12888	P70399
RefSeq (mRNA)	NM_001141979	NM_001290830
RefSeq (protein)	NP_001135451	NP_001277759
Location (UCSC)	Chr 15: 43.4 – 43.51 Mb	Chr 2: 121.19 – 121.27 Mb
PubMed search

Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.^[1][2][3]

Clinical significance

53BP1 is underexpressed in most cases of triple-negative breast cancer.^[4]

Interactions

53BP1 has been shown to interact with:

• Ataxia telangiectasia mutated,^[5][6]
• Bloom syndrome protein,^[7]
• DYNLL1,^[8]
• E2F1,^[9]
• H2AFX^[5][6][7]
• Histone H4 dimethylated or monomethylated at Lysine 20,^[10]
• PAXIP1,^[11][12]
• RPA2,^[13]
• Replication protein A1,^[13] and
• p53,^{[1][14][7][15][8][16][17]}

References

1. Iwabuchi K, Bartel PL, Li B, Marraccino R, Fields S (Jun 1994). "Two cellular proteins that bind to wild-type but not mutant p53". Proceedings of the National Academy of Sciences of the United States of America 91 (13): 6098–102. doi:10.1073/pnas.91.13.6098. PMC 44145. PMID 8016121.
2. Iwabuchi K, Li B, Massa HF, Trask BJ, Date T, Fields S (Oct 1998). "Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2". The Journal of Biological Chemistry 273 (40): 26061–8. doi:10.1074/jbc.273.40.26061. PMID 9748285.
3. "Entrez Gene: TP53BP1 tumor protein p53 binding protein 1".
4. Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, Hiddingh S, Thanasoula M, Kulkarni A, Yang Q, Haffty BG, Tommiska J, Blomqvist C, Drapkin R, Adams DJ, Nevanlinna H, Bartek J, Tarsounas M, Ganesan S, Jonkers J (Jun 2010). "53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers". Nature Structural & Molecular Biology 17 (6): 688–95. doi:10.1038/nsmb.1831. PMC 2912507. PMID 20453858.
5. Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, Naka K, Xia Z, Camerini-Otero RD, Motoyama N, Carpenter PB, Bonner WM, Chen J, Nussenzweig A (Dec 2002). "DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1". Nature Cell Biology 4 (12): 993–7. doi:10.1038/ncb884. PMID 12447390.
6. Ward IM, Minn K, Jorda KG, Chen J (May 2003). "Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX". The Journal of Biological Chemistry 278 (22): 19579–82. doi:10.1074/jbc.C300117200. PMID 12697768.
7. Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC (Sep 2004). "Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest". The Journal of Cell Biology 166 (6): 801–13. doi:10.1083/jcb.200405128. PMC 2172115. PMID 15364958.
8. Lo KW, Kan HM, Chan LN, Xu WG, Wang KP, Wu Z, Sheng M, Zhang M (Mar 2005). "The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation". The Journal of Biological Chemistry 280 (9): 8172–9. doi:10.1074/jbc.M411408200. PMID 15611139.
9. Choubey D, Li SJ, Datta B, Gutterman JU, Lengyel P (Oct 1996). "Inhibition of E2F-mediated transcription by p202". The EMBO Journal 15 (20): 5668–78. PMC 452311. PMID 8896460.
10. Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G (Dec 2006). "Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair". Cell 127 (7): 1361–73. doi:10.1016/j.cell.2006.10.043. PMC 1804291. PMID 17190600.
11. Jowsey PA, Doherty AJ, Rouse J (Dec 2004). "Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation". The Journal of Biological Chemistry 279 (53): 55562–9. doi:10.1074/jbc.M411021200. PMID 15456759.
12. Manke IA, Lowery DM, Nguyen A, Yaffe MB (Oct 2003). "BRCT repeats as phosphopeptide-binding modules involved in protein targeting". Science 302 (5645): 636–9. doi:10.1126/science.1088877. PMID 14576432.
13. Yoo E, Kim BU, Lee SY, Cho CH, Chung JH, Lee CH (Aug 2005). "53BP1 is associated with replication protein A and is required for RPA2 hyperphosphorylation following DNA damage". Oncogene 24 (35): 5423–30. doi:10.1038/sj.onc.1208710. PMID 15856006.
14. Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ (Jul 2002). "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor". The EMBO Journal 21 (14): 3863–72. doi:10.1093/emboj/cdf383. PMC 126127. PMID 12110597.
15. Ekblad CM, Friedler A, Veprintsev D, Weinberg RL, Itzhaki LS (Mar 2004). "Comparison of BRCT domains of BRCA1 and 53BP1: a biophysical analysis". Protein Science 13 (3): 617–25. doi:10.1110/ps.03461404. PMC 2286730. PMID 14978302.
16. Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP (Mar 2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development 16 (5): 583–93. doi:10.1101/gad.959202. PMC 155350. PMID 11877378.
17. Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ (Oct 2002). "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor". Acta Crystallographica. Section D, Biological Crystallography 58 (Pt 10 Pt 2): 1826–9. PMID 12351827.

Further reading

• Choubey D, Lengyel P (Mar 1995). "Binding of an interferon-inducible protein (p202) to the retinoblastoma protein". The Journal of Biological Chemistry 270 (11): 6134–40. doi:10.1074/jbc.270.11.6134. PMID 7890747.
• Choubey D, Li SJ, Datta B, Gutterman JU, Lengyel P (Oct 1996). "Inhibition of E2F-mediated transcription by p202". The EMBO Journal 15 (20): 5668–78. PMC 452311. PMID 8896460.
• Datta B, Li B, Choubey D, Nallur G, Lengyel P (Nov 1996). "p202, an interferon-inducible modulator of transcription, inhibits transcriptional activation by the p53 tumor suppressor protein, and a segment from the p53-binding protein 1 that binds to p202 overcomes this inhibition". The Journal of Biological Chemistry 271 (44): 27544–55. doi:10.1074/jbc.271.44.27544. PMID 8910340.
• Wen Y, Yan DH, Spohn B, Deng J, Lin SY, Hung MC (Jan 2000). "Tumor suppression and sensitization to tumor necrosis factor alpha-induced apoptosis by an interferon-inducible protein, p202, in breast cancer cells". Cancer Research 60 (1): 42–6. PMID 10646849.
• Xia Z, Morales JC, Dunphy WG, Carpenter PB (Jan 2001). "Negative cell cycle regulation and DNA damage-inducible phosphorylation of the BRCT protein 53BP1". The Journal of Biological Chemistry 276 (4): 2708–18. doi:10.1074/jbc.M007665200. PMID 11042216.
• Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP (Mar 2002). "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development 16 (5): 583–93. doi:10.1101/gad.959202. PMC 155350. PMID 11877378.
• Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ (Jul 2002). "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor". The EMBO Journal 21 (14): 3863–72. doi:10.1093/emboj/cdf383. PMC 126127. PMID 12110597.
• Lai H, Lin L, Nadji M, Lai S, Trapido E, Meng L (2002). "Mutations in the p53 tumor suppressor gene and early onset breast cancer". Cancer Biology & Therapy 1 (1): 31–6. doi:10.4161/cbt.1.1.37. PMID 12170762.
• Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ (Oct 2002). "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor". Acta Crystallographica. Section D, Biological Crystallography 58 (Pt 10 Pt 2): 1826–9. doi:10.1107/S0907444902010910. PMID 12351827.
• Wang B, Matsuoka S, Carpenter PB, Elledge SJ (Nov 2002). "53BP1, a mediator of the DNA damage checkpoint". Science 298 (5597): 1435–8. doi:10.1126/science.1076182. PMID 12364621.
• Richie CT, Peterson C, Lu T, Hittelman WN, Carpenter PB, Legerski RJ (Dec 2002). "hSnm1 colocalizes and physically associates with 53BP1 before and after DNA damage". Molecular and Cellular Biology 22 (24): 8635–47. doi:10.1128/MCB.22.24.8635-8647.2002. PMC 139863. PMID 12446782.
• DiTullio RA, Mochan TA, Venere M, Bartkova J, Sehested M, Bartek J, Halazonetis TD (Dec 2002). "53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer". Nature Cell Biology 4 (12): 998–1002. doi:10.1038/ncb892. PMID 12447382.
• Fernandez-Capetillo O, Chen HT, Celeste A, Ward I, Romanienko PJ, Morales JC, Naka K, Xia Z, Camerini-Otero RD, Motoyama N, Carpenter PB, Bonner WM, Chen J, Nussenzweig A (Dec 2002). "DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1". Nature Cell Biology 4 (12): 993–7. doi:10.1038/ncb884. PMID 12447390.
• Peng A, Chen PL (Mar 2003). "NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage". The Journal of Biological Chemistry 278 (11): 8873–6. doi:10.1074/jbc.C300001200. PMID 12551934.
• Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ (Feb 2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". Nature 421 (6926): 961–6. doi:10.1038/nature01446. PMID 12607005.
• Yan DH, Abramian A, Li Z, Ding Y, Wen Y, Liu TJ, Hunt K (Mar 2003). "P202, an interferon-inducible protein, inhibits E2F1-mediated apoptosis in prostate cancer cells". Biochemical and Biophysical Research Communications 303 (1): 219–22. doi:10.1016/S0006-291X(03)00320-6. PMID 12646190.
• Kao GD, McKenna WG, Guenther MG, Muschel RJ, Lazar MA, Yen TJ (Mar 2003). "Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response". The Journal of Cell Biology 160 (7): 1017–27. doi:10.1083/jcb.200209065. PMC 2172769. PMID 12668657.