title: The negative cell cycle regulator, Tob (transducer of ErbB-2), is a multifunctional protein involved in hippocampus-dependent learning and memory.
abstract: Tob (transducer of ErbB2) is a negative cell cycle regulator with anti-proliferative activity in the periphery. Using a behavioral screening paradigm to look for novel gene functions in the brain, we identified Tob as a brain-expressed protein involved in learning and memory. Behavioral training of fear-conditioning triggered a transient elevation of Tob protein, which preceded the formation of long-term memory. Functional perturbation of Tob by intra-CA1 infusion of antisense oligonucleotides in rats impaired spatial learning and memory in the Morris water maze and long-term memory for contextual fear conditioning, two behavioral paradigms that require the hippocampus. Furthermore, long-term potentiation was suppressed by Tob antisense infusion into the CA1 region. Together, these results indicate that the negative cell cycle regulator Tob is a multifunctional protein involved in hippocampus-dependent learning and memory.
authors.affiliation: Research Center of Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 500 Cao-Bao Road, Shanghai 200233, China.
authors.forename: M
authors.initials: M
authors.lastname: Jin
authors.forename: X-M
authors.initials: XM
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Tu
authors.forename: X-H
authors.initials: XH
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: N
authors.initials: N
authors.lastname: Guo
authors.forename: Z
authors.initials: Z
authors.lastname: Xie
authors.forename: G
authors.initials: G
authors.lastname: Zhao
authors.forename: N
authors.initials: N
authors.lastname: Jing
authors.forename: B-M
authors.initials: BM
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology*; D001483:Base Sequence; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000502:physiology*; D003001:Cloning, Molecular; D003214:Conditioning, Classical / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005239:Fear; D015870:Gene Expression / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D015723:Gene Library; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D018782:Maze Learning; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009841:Oligonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C490903:Tob1 protein, mouse