title: Structural and functional characterization of the acidic region from the RIZ tumor suppressor.
abstract: RIZ (retinoblastoma protein-interacting zinc finger protein), also denoted PRDM2, is a transcriptional regulator and tumor suppressor. It was initially identified because of its ability to interact with another well-established tumor suppressor, the retinoblastoma protein (Rb). A short motif, IRCDE, in the acidic region (AR) of RIZ was reported to play an important role in the interaction with the pocket domain of Rb. The IRCDE motif is similar to a consensus Rb-binding sequence LXCXE (where X denotes any amino acid) that is found in several viral Rb-inactivating oncoproteins. To improve our understanding of the molecular basis of binding of Rb to RIZ, we investigated the interaction between purified recombinant AR and the pocket domain of Rb using nuclear magnetic resonance spectroscopy, isothermal titration calorimetry, and fluorescence anisotropy experiments. We show that AR is intrinsically disordered and that it binds the pocket domain with submicromolar affinity. We also demonstrate that the interaction between AR and the pocket domain is mediated primarily by the short stretch of residues containing the IRCDE motif and that the contribution of other parts of AR to the interaction with the pocket domain is minimal. Overall, our data provide clear evidence that RIZ is one of the few cellular proteins that can interact directly with the LXCXE-binding cleft on Rb.
authors: Department of Chemistry and Biochemistry, University of Montana , Missoula, Montana 59812, United States.
authors: Yizhi
authors: Y
authors: Sun
authors: Jessica M
authors: JM
authors: Stine
authors: Daniel Z
authors: DZ
authors: Atwater
authors: Ayesha
authors: A
authors: Sharmin
authors: J B Alexander
authors: JB
authors: Ross
authors: Klára
authors: K
authors: Briknarová
mesh_terms: D000595:Amino Acid Sequence; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D015513:Oncogene Proteins
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