Identification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner.
Tankyrase-1 and -2 are closely related poly(ADP-ribose) polymerases that use an ankyrin-repeat domain to bind diverse proteins, including TRF (telomere-repeat binding factor)-1, IRAP (insulin-responsive aminopeptidase), and TAB182 (182-kDa tankyrase-binding protein). TRF1 binding allows tankyrase to regulate telomere dynamics in human cells, whereas IRAP binding presumably allows tankyrase to regulate the targeting of IRAP. The mechanism by which tankyrase binds to diverse proteins has not been investigated. Herein we describe a novel RXXPDG motif shared by IRAP, TAB182, and human TRF1 that mediates their binding to tankyrases. Interestingly, mouse TRF1 lacks this motif and thus does not bind either tankyrase-1 or -2. Using the ankyrin domain of tankyrase as a bait in a yeast two-hybrid screen, we also found the RXXPDG motif in six candidate tankyrase partners, including the nuclear/mitotic apparatus protein (NuMA). We verified NuMA as an RXXPDG-mediated partner of tankyrase and suggest that this interaction contributes to the known colocalization of tankyrase and NuMA at mitotic spindle poles.
Sbodio
Juan I
JI
Department of Medicine, University of California San Diego, La Jolla, California 92093-0673, USA.
Chi
Nai-Wen
NW
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002645:Chickens; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012795:Sialoglycoproteins / Q000737:chemistry / Q000378:metabolism*; D013045:Species Specificity; D038501:Tankyrases; D035321:Telomeric Repeat Binding Protein 1
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011065:Poly(ADP-ribose) Polymerases; D012795:Sialoglycoproteins; D038501:Tankyrases; D035321:Telomeric Repeat Binding Protein 1; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; C455625:TNKS1BP1 protein, human; C498822:Tnks protein, mouse; C418109:TNKS protein, human