The 8-kDa Dynein Light Chain Binds to p53-binding Protein 1 and Mediates DNA Damage-induced p53 Nuclear Accumulation

The tumor suppressor protein p53 is known to undergo cytoplasmic dynein-dependent nuclear translocation in response to DNA damage. However, the molecular link between p53 and the minus end-directed microtubule motor dynein complex has not been described. We report here that the 8-kDa light chain (LC8) of dynein binds to p53-binding protein 1 (53BP1). The LC8-binding domain was mapped to a short peptide segment immediately N-terminal to the kinetochore localization region of 53BP1. The LC8-binding domain is completely separated from the p53-binding domain in 53BP1. Therefore, 53BP1 can potentially act as an adaptor to assemble p53 to the dynein complex. Unlike other known LC8-binding proteins, 53BP1 contains two distinct LC8-binding motifs that are arranged in tandem. We that 53BP1 can the dynein complex. of the between and 53BP1 in DNA nuclear of that is to as a to link a of molecular to the dynein The tumor suppressor protein p53 is known to undergo cytoplasmic dynein-dependent nuclear translocation in response to DNA damage. However, the molecular link between p53 and the minus end-directed microtubule motor dynein complex has not been described. We report here that the 8-kDa light chain (LC8) of dynein binds to p53-binding protein 1 (53BP1). The LC8-binding domain was mapped to a short peptide segment immediately N-terminal to the kinetochore localization region of 53BP1. The LC8-binding domain is completely separated from the p53-binding domain in 53BP1. Therefore, 53BP1 can potentially act as an adaptor to assemble p53 to the dynein complex. Unlike other known LC8-binding proteins, 53BP1 contains two distinct LC8-binding motifs that are arranged in tandem. We that 53BP1 can the dynein complex. of the between and 53BP1 in DNA nuclear of that is to as a to link a of molecular to the dynein 53BP1 p53-binding protein dynein 8-kDa dynein light p53-binding protein dynein 8-kDa dynein light is a nuclear protein that was as a protein in a The protein was as an of The of 53BP1 contains two a protein in a of in of and DNA The of 53BP1 are to p53 and of the a a to are motifs in the N-terminal region of and of motifs been to of has been that 53BP1 as an adaptor protein in the and and response to DNA p53 in the a of and that are in and The DNA nuclear localization of p53 the minus end-directed microtubule motor dynein of the motor of dynein of an the chain of the motor in of p53 in the DNA The molecular of p53 nuclear is p53 is not known to to the dynein motor complex. that adaptor can act as a to p53 to the dynein of adaptor the p53 nuclear was that complex act as an adaptor to link p53 to a of the dynein motor complex in dynein is a protein complex of two to a The of the motor complex contains two light and light The 8-kDa light chain and is a of the cytoplasmic dynein complex has been and has been to to a of was to to to the of the and to the of the to to protein to and to a of has been that as a adaptor that to the dynein motor report that binds to 53BP1. that 53BP1 contains two distinct LC8-binding motifs that are arranged in tandem. of the and that 53BP1 can to link p53 to the dynein complex. of the between and 53BP1 in DNA nuclear of The in a distinct p53 nuclear was as was and to of a in the 53BP1 an N-terminal and a and of 53BP1 The p53 was of 53BP1 and the DNA the of the The was DNA the The p53 was the p53 the of an and of of was as the the in to an of of the protein was the of to a of The in and the The to the The of the the of was the a The N-terminal of the protein was The and other the a of has been in and and in and in a a to and an of DNA a the of was to was from was to and was from to a in a in and an was of 53BP1 53BP1 The The and The and The of the between and the as in and The of the to the protein domain of and and and of the and was to the to a of and the and The and of 53BP1 as a LC8-binding of a as the was to LC8-binding a of 53BP1 The between and 53BP1 was in an in in the 53BP1 from the was to 1 in the 53BP1 and to 1 in the the two in 53BP1 and a complex that from LC8-binding of 53BP1 from the the domain of the of the that the domain a peptide to of 53BP1. was to to 1 in the of from the 53BP1 completely to 1 in the the in 1 that 53BP1 can to and the N-terminal to the domain is and 53BP1 to to LC8-binding that binds to a is and of the that the the LC8-binding of 53BP1 LC8-binding the is the LC8-binding of from the LC8-binding of 53BP1 and that of the from the was to LC8-binding the of 53BP1 to that the is not the LC8-binding is not the LC8-binding is known that not the in LC8-binding the of a in the of the to We that LC8-binding contains two motifs and that motifs are in and The LC8-binding of 53BP1 contains a is of the and the of 53BP1 an in the from the LC8-binding segment of 53BP1 and the LC8-binding of the and of the the to the of 53BP1 the of other of 53BP1 in We a the and the that 53BP1 contains two distinct LC8-binding motifs of and contains two distinct LC8-binding of LC8-binding from the The of 53BP1 is the of motifs of LC8-binding The of 53BP1 is the of the the to the of the The of the two motifs are in the of the between and The as a that the of 53BP1 binds to in an as the that of the in the to an to Therefore, not to the between the of 53BP1 and in the of the between the of 53BP1 and of the between and the LC8-binding domain of LC8-binding protein an We the between the of 53BP1 and in the of the to a peptide to of 53BP1 the and the peptide the of of the two distinct of in the of two of to the and the of The of the and the of in the that the binds to The was of a two of the that binds to two of the The of the of the to was the between the and the 53BP1 to of 53BP1 binds to of the of and the The of the is and as a of the of and of the The and are and of and of and the protein in complex the The to the and is The of is the of the The the of the of mapped to the of the of LC8-binding motifs 53BP1 to the 53BP1 in a to the of the in the a peptide was the in The of was to of the and the in the to 53BP1 in a as the of the the in the completely the LC8-binding of the of are in the We the to the region the of of the of the of the The in the mapped to the of the The that in the and the N-terminal of are in the The of is to that the LC8-binding peptide from Therefore, that the of 53BP1 is to to the of the of the LC8-binding in a of proteins, and a and the LC8-binding domain and the p53-binding domain 53BP1 not that 53BP1 as a protein p53 and a protein complex. the complex and We the domain of p53 the as is known to to 53BP1 in that can to p53 and can to p53 two are and was between p53 and the in can p53 53BP1 is in and p53 can of the that the can and p53 that can as a that not p53 that binds to 53BP1 in not to p53 in the that p53 and 53BP1 in can 53BP1 as as p53 1 in and to that not to 53BP1 to of 53BP1 the dynein complex. 53BP1 was in of 53BP1 the chain and the of the cytoplasmic dynein complex. 1 in that an the 53BP1 can the dynein complex. is a between the complex and the dynein has been to to a of other the dynein complex. We in and that the chain as as the of the cytoplasmic dynein complex the in that is of the 53BP1 to the dynein complex in DNA p53 has been that the dynein is DNA p53 nuclear However, the molecular of the dynein-dependent nuclear of p53 has not been described. The of the complex in that link the complex to the dynein of the dynein-dependent p53 nuclear the between and a peptide of to as peptide contains the and binds to the of the peptide was to the in a peptide the and in the the was not to the the of the complex in p53 nuclear in the peptide to the of the domain of are to of of of the peptide in the in of p53 nuclear that the of p53 nuclear is a peptide of in the p53 in the in the of the and nuclear localization of p53 the peptide was of the and and of the in the to not to of p53 nuclear a p53 in and the peptide was in the that the the of the peptide to of We that the peptide a of nuclear not of the p53 nuclear of the of in the of peptide in the The in the the of in the of The the of in the the of the of the of nuclear the The of cytoplasmic peptide was The peptide to the of the of and The are the of that 53BP1 is a of the light chain of cytoplasmic We that 53BP1 can act as an adaptor to assemble p53 and a complex. that 53BP1 can the dynein complex. 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to the microtubule a molecular p53 nuclear of the between 53BP1 and the dynein in a LC8-binding peptide DNA p53 nuclear is that the p53 from of between and other the dynein that the of is not dynein was that the complex can as an adaptor to p53 to the dynein motor in the of is not that molecular are in p53 to in response to is a protein The protein as an of to a of in the and and can that the protein 53BP1 are and that molecular as dynein to in 53BP1 is in the is that the dynein complex an in 53BP1 the are to 53BP1 p53-binding protein dynein 8-kDa dynein light p53-binding protein dynein 8-kDa dynein light is a nuclear protein that was as a protein in a The protein was as an of The of 53BP1 contains two a protein in a of in of and DNA The of 53BP1 are to p53 and of the a a to are motifs in the N-terminal region of and of motifs been to of has been that 53BP1 as an adaptor protein in the and and response to DNA p53 in the a of and that are in and The DNA nuclear localization of p53 the 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and The LC8-binding of 53BP1 contains a is of the and the of 53BP1 an in the from the LC8-binding segment of 53BP1 and the LC8-binding of the and of the the to the of 53BP1 the of other of 53BP1 in We a the and the that 53BP1 contains two distinct LC8-binding motifs of and that the of 53BP1 binds to in an as the that of the in the to an to Therefore, not to the between the of 53BP1 and in the of the between the of 53BP1 and of the between and the LC8-binding domain of LC8-binding protein an We the between the of 53BP1 and in the of the to a peptide to of 53BP1 the and the peptide the of of the two distinct of in the of two of to the and the of The of the and the of in the that the binds to The was of a two of the that binds to two of the The of the of the to was the between the and the 53BP1 to of 53BP1 binds to of the of and the The of the is and as a of the of and of the The and are and of and of and the protein in complex the The to the and is The of is the of the The the of the of mapped to the of the of LC8-binding motifs 53BP1 to the 53BP1 in a to the of the in the a peptide was the in The of was to of the and the in the to 53BP1 in a as the of the the in the completely the LC8-binding of the of are in the We the to the region the of of the of the of the The in the mapped to the of the The that in the and the N-terminal of are in the The of is to that the LC8-binding peptide from Therefore, that the of 53BP1 is to to the of the of the LC8-binding in a of proteins, and a and the LC8-binding domain and the p53-binding domain 53BP1 not that 53BP1 as a protein p53 and a protein complex. the complex and We the domain of p53 the as is known to to 53BP1 in that can to p53 and can to p53 two are and was between p53 and the in can p53 53BP1 is in and p53 can of the that the can and p53 that can as a that not p53 that binds to 53BP1 in not to p53 in the that p53 and 53BP1 in can 53BP1 as as p53 1 in and to that not to 53BP1 to of 53BP1 the dynein complex. 53BP1 was in of 53BP1 the chain and the of the cytoplasmic dynein complex. 1 in that an the 53BP1 can the dynein complex. is a between the complex and the dynein has been to to a of other the dynein complex. We in and that the chain as as the of the cytoplasmic dynein complex the in that is of the 53BP1 to the dynein complex in DNA p53 has been that the dynein is DNA p53 nuclear However, the molecular of the dynein-dependent nuclear of p53 has not been described. 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We in and that the chain as as the of the cytoplasmic dynein complex the in that is of the 53BP1 to the dynein complex in The DNA p53 has been that the dynein is DNA p53 nuclear However, the molecular of the dynein-dependent nuclear of p53 has not been described. The of the complex in that link the complex to the dynein of the dynein-dependent p53 nuclear the between and a peptide of to as peptide contains the and binds to the of the peptide was to the in a peptide the and in the the was not to the the of the complex in p53 nuclear in the peptide to the of the domain of are to of of of the peptide in the in of p53 nuclear that the of p53 nuclear is a peptide of in the p53 in the in the of the and nuclear localization of p53 the peptide was of the and and of the in the to not to of p53 nuclear a p53 in and the peptide was in the that the the of the peptide to of We that the peptide a of nuclear not that 53BP1 is a of the light chain of cytoplasmic We that 53BP1 can act as an adaptor to assemble p53 and a complex. that 53BP1 can the dynein complex. We that 53BP1 is a LC8-binding known LC8-binding 53BP1 contains two distinct LC8-binding motifs and The motifs are of the domain and not known protein 53BP1. the two LC8-binding is to the that of the to an in the a the of the peptide to Therefore, the peptide the of 53BP1 is to a LC8-binding The other LC8-binding the LC8-binding in and We that the LC8-binding in to the of the LC8-binding to the between and a of is that 53BP1 contains two distinct LC8-binding motifs in 53BP1. and that are to to and and The is to the dynein motor to the of the dynein chain of two has been that the other of the is to to to the dynein complex LC8-binding 53BP1 to to the dynein is that of the LC8-binding motifs from is in the 53BP1 The other two LC8-binding immediately to other protein is to the that 53BP1 is to the dynein complex. in that the 53BP1 and LC8-binding to However, not to between 53BP1 and to the of the of 53BP1 as a of the dynein complex that 53BP1 can as an adaptor protein of p53 as as other to the microtubule a molecular p53 nuclear of the between 53BP1 and the dynein in a LC8-binding peptide DNA p53 nuclear is that the p53 from of between and other the dynein that the of is not dynein was that the complex can as an adaptor to p53 to the dynein motor in the of is not that molecular are in p53 to in response to is a protein The protein as an of to a of in the and and can that the protein 53BP1 are and that molecular as dynein to in 53BP1 is in the is that the dynein complex an in 53BP1 the are to that 53BP1 is a of the light chain of cytoplasmic We that 53BP1 can act as an adaptor to assemble p53 and a complex. that 53BP1 can the dynein complex. We that 53BP1 is a LC8-binding known LC8-binding 53BP1 contains two distinct LC8-binding motifs and The motifs are of the domain and not known protein 53BP1. the two LC8-binding is to the that of the to an in the a the of the peptide to Therefore, the peptide the of 53BP1 is to a LC8-binding The other LC8-binding the LC8-binding in and We that the LC8-binding in to the of the LC8-binding to the between and a of is that 53BP1 contains two distinct LC8-binding motifs in 53BP1. and that are to to and and The is to the dynein motor to the of the dynein chain of two has been that the other of the is to to to the dynein complex LC8-binding 53BP1 to to the dynein is that of the LC8-binding motifs from is in the 53BP1 The other two LC8-binding immediately to other protein is to the that 53BP1 is to the dynein complex. in that the 53BP1 and LC8-binding to However, not to between 53BP1 and to the of the 53BP1. The of 53BP1 as a of the dynein complex that 53BP1 can as an adaptor protein of p53 as as other to the microtubule a molecular p53 nuclear of the between 53BP1 and the dynein in a LC8-binding peptide DNA p53 nuclear is that the p53 from of between and other the dynein that the of is not dynein was that the complex can as an adaptor to p53 to the dynein motor in the of is not that molecular are in p53 to in response to 53BP1 is a protein The protein as an of to a of in the and and can that the protein 53BP1 are and that molecular as dynein to in 53BP1 is in the is that the dynein complex an in 53BP1 the are to We and the 53BP1 and the