Differential Association of Products of Alternative Transcripts of the Candidate Tumor Suppressor ING1 with the mSin3/HDAC1 Transcriptional Corepressor Complex*

The candidate tumor suppressor ING1was identified in a genetic screen aimed at isolation of human genes whose expression is suppressed in cancer cells. It may function as a negative growth regulator in the p53 signal transduction pathway. However, its molecular mechanism is not clear. The ING1locus encodes alternative transcripts of p47 ING1a , p33 ING1b , and p24 ING1c . Here we report differential association of protein products of ING1 with the mSin3 transcriptional corepressor complex. p33 ING1b associates with Sin3, SAP30, HDAC1, RbAp48, and other proteins, to form large protein complexes, whereas p24 ING1c does not. The ING1 immune complexes are active in deacetylating core histones in vitro, and p33 ING1b is functionally associated with HDAC1-mediated transcriptional repression in transfected cells. Our data provide basis for a p33 ING1b -specific molecular mechanism for the function of the ING1 locus.

[1]  S. Nishioka,et al.  Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. , 2000, Cancer research.

[2]  T. Furukawa,et al.  p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1 , 2000, Journal of Human Genetics.

[3]  R. Eisenman,et al.  Sin Meets NuRD and Other Tails of Repression , 1999, Cell.

[4]  E. Koonin,et al.  Structure and Regulation of the Mouse ing1 Gene , 1999, The Journal of Biological Chemistry.

[5]  I. Garkavtsev.  Correction: Suppression of the novel growth inhibitor p33 ING1 promotes neoplastic transformation , 1999 .

[6]  P. Watson,et al.  Suppression of ING1 expression in sporadic breast cancer , 1999, Oncogene.

[7]  A. Bird,et al.  Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. , 1999, Genes & development.

[8]  T. Kouzarides,et al.  Retinoblastoma protein meets chromatin. , 1999, Trends in biochemical sciences.

[9]  Jun Qin,et al.  Histone-like TAFs within the PCAF Histone Acetylase Complex , 1998, Cell.

[10]  D. Reinberg,et al.  SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex. , 1998, Molecular cell.

[11]  K. Struhl.  Histone acetylation and transcriptional regulatory mechanisms. , 1998, Genes & development.

[12]  D. Dean,et al.  Rb Interacts with Histone Deacetylase to Repress Transcription , 1998, Cell.

[13]  L. Magnaghi-Jaulin,et al.  Retinoblastoma protein represses transcription by recruiting a histone deacetylase , 1998, Nature.

[14]  I. Garkavtsev,et al.  The candidate tumour suppressor p33ING1cooperates with p53 in cell growth control , 1998, Nature.

[15]  P. Vogt,et al.  Oncogenic transformation induced by the Qin protein is correlated with transcriptional repression. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  D. Reinberg,et al.  Histone Deacetylases and SAP18, a Novel Polypeptide, Are Components of a Human Sin3 Complex , 1997, Cell.

[17]  I. Garkavtsev,et al.  Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor , 1997, Molecular and cellular biology.

[18]  I. Garkavtsev,et al.  Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation , 1996, Nature Genetics.

[19]  M. Grunstein,et al.  HDA1 and HDA3 Are Components of a Yeast Histone Deacetylase (HDA) Complex* , 1996, The Journal of Biological Chemistry.

[20]  R. Maestro,et al.  Chromosome 13q deletion mapping in head and neck squamous cell carcinomas: identification of two distinct regions of preferential loss. , 1996, Cancer research.

[21]  R. Eisenman,et al.  Mad-max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3 , 1995, Cell.

[22]  L. Chin,et al.  An amino-terminal domain of Mxi1 mediates anti-myc oncogenic activity and interacts with a homolog of the Yeast Transcriptional Repressor SIN3 , 1995, Cell.

[23]  T. Gibson,et al.  The PHD finger: implications for chromatin-mediated transcriptional regulation. , 1995, Trends in biochemical sciences.

[24]  C. Hauser,et al.  Oncogenic Ras can induce transcriptional activation through a variety of promoter elements, including tandem c-Ets-2 binding sites. , 1994, Oncogene.

[25]  K. Helin,et al.  Characterization of the retinoblastoma binding proteins RBP1 and RBP2. , 1993, Oncogene.

[26]  J. Manley,et al.  Functional domains of the Drosophila Engrailed protein. , 1993, The EMBO journal.

[27]  K. V. van Holde,et al.  Histone hyperacetylation: its effects on nucleosome conformation and stability. , 1986, Biochemistry.

[28]  R. Reeves,et al.  Sodium butyrate inhibits histone deacetylation in cultured cells , 1978, Cell.

[29]  J. Qin,et al.  A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. , 1999, Molecular cell.

[30]  D. Demetrick,et al.  Cellular localization and chromosome mapping of a novel candidate tumor suppressor gene (ING1). , 1997, Cytogenetics and cell genetics.