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Table 1 Summary of proteins known to interact with 53BP1.

From: Tying the loose ends together in DNA double strand break repair with 53BP1

Protein

Comments

References

p53

53BP1 was discovered as a protein that binds to the central core DNA binding domain of p53 in a yeast two-hybrid assay.

[3]

RIF1

53BP1 is required for IRIF formation of RIF1, a human homolog of a yeast telomeric protein that participates in the intra S-phase checkpoint.

[104]

RPA2

53BP1 co-immunoprecipitates with RPA2, single-stranded DNA binding complex. Association is IR dependent.

[105]

Jab1

Jab1 was shown to bind to 53BP1 in a yeas two-hybrid screen. Jab1 may be responsible for the observed hyperphosphorylation of 53BP1 in M phase in response to nocodazole.

[93]

Dynein LC8

53BP1 possesses two tandem LC8 binding sites (Fig. 1) and may bind to the dynein motor complex protein in a manner that regulates p53 function.

[16]

BRCA1

53BP1 is required for optimal IR-inducible phosphorylation of BRCA1 at S1472; 53BP1 is part of the "BASC" complex and interacts with other components of this complex.

[13, 106]

Chk2

53BP1 is possibly required for optimal Chk2 phosphorylation at T68 in response to IR.

[13, 29]

H2AX

A fragment of 53BP1 containing residues 956–1354 were reported to bind phosphorylated peptides corresponding to the C-terminal tail of γ-H2AX.

[107]

Mdc1

53BP1 binds to the BRCT repeat protein Mdc1. 53BP1 IRIF formation is dependent upon functional Mdc1.

[38–40, 50]

Smn1

53BP1 co-localizes with and co-immunoprecipitates with Smn1, an Artemis-like protein.

[108]

Artemis

53BP1-Artemis interactions were reported from cells transfected with 53BP1 expression vectors

[88]

ATM

53BP1 has been reported to co-immunoprecipitate with ATM. 53BP1 is clearly an ATM substrate, but may also participate upstream of ATM activation

[11, 23, 26, 28, 58]

Histones H3 and H4

The tandem Tudor domains of 53BP1 have been reported to bind various methylated states of histones H3 and H4 as discussed in the text.

[58, 60]

Rad51

Although 53BP1 does not appear to function in break-induced IR, it has been detected to co-localize to I-SceI induced DSBs.

[52, 53]

HDAC4

53BP1 and HDAC4 bind together and co-localize to IRIF. The stability of 53BP1 depends on HDAC4 and vice versa.

[18]

PTIP

PTIP shows increased association with 53BP1 in response to IR and in an ATM-dependent manner. Amino acids 1052–1710 of 53BP1 are necessary for interaction with PTIP.

[41]

USP28

Deubiquitinase that binds to 53BP1 and controls Chk2-p53-PUMA pathway. Also, mediates cytotoxic effects of nutlin, a molecule that influences p53 stability.

[20, 21]

  1. 53BP1 interacts with various factors implicated in maintaining genomic stability through their control of DSB repair, cell cycle checkpoints, and chromatin structure. Partial summary of proteins, listed in no particular order, reported to interact with 53BP1 throughout various in vitro and in vivo techniques including yeast-two hybrid assays and co-immunoprecipitation. See text for more details.