Differences in expression, actions and cocaine regulation of two isoforms for the brain transcriptional regulator NACl

被引:21
作者
Korutla, L
Wang, PJ
Lewis, DM
Neustadter, JH
Stromberg, MF
Mackler, SA [1 ]
机构
[1] Philadelphia VAMC, Med Res Serv 151C, Dept Med, Philadelphia, PA 19104 USA
[2] Philadelphia VAMC, Med Res Serv 151C, Dept Psychiat, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA
[5] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA
关键词
BTB/POZ; cocaine; RT-PCR; cDNA; transcription factor;
D O I
10.1016/S0306-4522(01)00518-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
BTB/POZ proteins can influence the cell cycle and contribute to oncogenesis. Many family members are present in the mammalian CNS. Previous work demonstrated elevated NAC1 mRNA levels in the rat nucleus accumbens in response to cocaine. NAC1 acts like other BTB/POZ proteins that regulate transcription but is unusual because of the absence of identifiable DNA binding domains. cDNAs were isolated encoding two NAC1 isoforms differing by only 27 amino acids (the longer isoform contains 514 amino acids). The mRNAs for both isoforms were simultaneously expressed throughout the rat brain and peripheral tissues. Semi-quantitative reverse transcript ion-polymerase chain reaction analysis revealed that the mRNA of the longer isoform was more abundant than the mRNA of the shorter isoform. Western blot analysis demonstrated a similar unequal distribution between the isoforms in the CNS. The longer isoform was the more abundant of the two NAC1 proteins and the ratio between them differed throughout the rat brain. The shorter isoform was not detected in most of the examined peripheral tissues, suggesting differences from the CNS in post-transcriptional processing, Both isoforms repressed transcription in H293T cells using a Gal4-luciferase reporter system. However, the shorter isoform did not repress transcription as effectively as the longer isoform, Transfection of different ratios for both isoforms, in order to replicate the relative amounts observed throughout the CNS, supported an interaction between the isoforms. The net effect on transcriptional repression was determined by the ratio of the two NAC1 isoforms. Each isoform exhibited the subnuclear localization that is characteristic of many BTB/POZ proteins. A rapid and transient increase in the level of the shorter isoform occurred in the nucleus accumbens 2 h following a single i.p. cocaine injection. We conclude that the two isoforms of NAC1 may differentially affect neuronal functions, including the regulation of cocaine-induced locomotion. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:421 / 429
页数:9
相关论文
共 16 条
[1]  
ALBAGLI O, 1995, CELL GROWTH DIFFER, V6, P1193
[2]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[3]   The promyelocytic leukemia zinc finger (PLZF) protein binds DNA in a high molecular weight complex associated with cdc2 kinase [J].
Ball, HJ ;
Melnick, A ;
Shaknovich, R ;
Kohanski, RA ;
Licht, JD .
NUCLEIC ACIDS RESEARCH, 1999, 27 (20) :4106-4113
[4]   THE POZ DOMAIN - A CONSERVED PROTEIN-PROTEIN INTERACTION MOTIF [J].
BARDWELL, VJ ;
TREISMAN, R .
GENES & DEVELOPMENT, 1994, 8 (14) :1664-1677
[5]  
Berhow MT, 1996, J NEUROSCI, V16, P4707
[6]  
Cha XY, 1997, J NEUROSCI, V17, P6864
[7]   BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor [J].
Chang, CC ;
Ye, BH ;
Chaganti, RSK ;
DallaFavera, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (14) :6947-6952
[8]   STUDIES ON MESOPOROUS MATERIALS .1. SYNTHESIS AND CHARACTERIZATION OF MCM-41 [J].
CHEN, CY ;
LI, HX ;
DAVIS, ME .
MICROPOROUS MATERIALS, 1993, 2 (01) :17-26
[9]   Regulation of a transcription factor network required for differentiation and metabolism [J].
Duncan, SA ;
Navas, MA ;
Dufort, D ;
Rossant, J ;
Stoffel, M .
SCIENCE, 1998, 281 (5377) :692-695
[10]   INDUCTION OF A LONG-LASTING AP-1 COMPLEX COMPOSED OF ALTERED FOS-LIKE PROTEINS IN BRAIN BY CHRONIC COCAINE AND OTHER CHRONIC TREATMENTS [J].
HOPE, BT ;
NYE, HE ;
KELZ, MB ;
SELF, DW ;
IADAROLA, MJ ;
NAKABEPPU, Y ;
DUMAN, RS ;
NESTLER, EJ .
NEURON, 1994, 13 (05) :1235-1244