The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding

K. M. Lee, W. I. Choi, D. I. Koh, Y. J. Kim, B. N. Jeon, J. H. Yoon, C. E. Lee, S. H. Kim, J. Oh, M. W. Hur

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box3 (bp,-55 to-63) and the MIZ-1-binding elements, MRE-A (bp,-90 to-64) and MRE-B (bp, 27 to 17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp,-95 to-100) and #3 (bp,-55 to-63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.

Original languageEnglish
Pages (from-to)1442-1458
Number of pages17
JournalOncogene
Volume31
Issue number11
DOIs
Publication statusPublished - 2012 Mar 15

Fingerprint

Competitive Binding
Oncogene Proteins
Zinc Fingers
Transcriptional Activation
Proteins
Histones
Biological Phenomena
Bone Neoplasms
Kidney Neoplasms
Chromatin Immunoprecipitation
B-Cell Lymphoma
Acetylation
Glutathione Transferase
Immunoprecipitation
Protein Binding
DNA Damage
Cell Cycle
Transcription Factors
Bone Marrow
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Lee, K. M. ; Choi, W. I. ; Koh, D. I. ; Kim, Y. J. ; Jeon, B. N. ; Yoon, J. H. ; Lee, C. E. ; Kim, S. H. ; Oh, J. ; Hur, M. W. / The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding. In: Oncogene. 2012 ; Vol. 31, No. 11. pp. 1442-1458.
@article{afea2dd594004dba9bc2ff060c2de5da,
title = "The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding",
abstract = "The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box3 (bp,-55 to-63) and the MIZ-1-binding elements, MRE-A (bp,-90 to-64) and MRE-B (bp, 27 to 17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp,-95 to-100) and #3 (bp,-55 to-63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.",
author = "Lee, {K. M.} and Choi, {W. I.} and Koh, {D. I.} and Kim, {Y. J.} and Jeon, {B. N.} and Yoon, {J. H.} and Lee, {C. E.} and Kim, {S. H.} and J. Oh and Hur, {M. W.}",
year = "2012",
month = "3",
day = "15",
doi = "10.1038/onc.2011.331",
language = "English",
volume = "31",
pages = "1442--1458",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "11",

}

Lee, KM, Choi, WI, Koh, DI, Kim, YJ, Jeon, BN, Yoon, JH, Lee, CE, Kim, SH, Oh, J & Hur, MW 2012, 'The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding', Oncogene, vol. 31, no. 11, pp. 1442-1458. https://doi.org/10.1038/onc.2011.331

The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding. / Lee, K. M.; Choi, W. I.; Koh, D. I.; Kim, Y. J.; Jeon, B. N.; Yoon, J. H.; Lee, C. E.; Kim, S. H.; Oh, J.; Hur, M. W.

In: Oncogene, Vol. 31, No. 11, 15.03.2012, p. 1442-1458.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The proto-oncoprotein KR-POK represses transcriptional activation of CDKN1A by MIZ-1 through competitive binding

AU - Lee, K. M.

AU - Choi, W. I.

AU - Koh, D. I.

AU - Kim, Y. J.

AU - Jeon, B. N.

AU - Yoon, J. H.

AU - Lee, C. E.

AU - Kim, S. H.

AU - Oh, J.

AU - Hur, M. W.

PY - 2012/3/15

Y1 - 2012/3/15

N2 - The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box3 (bp,-55 to-63) and the MIZ-1-binding elements, MRE-A (bp,-90 to-64) and MRE-B (bp, 27 to 17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp,-95 to-100) and #3 (bp,-55 to-63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.

AB - The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box3 (bp,-55 to-63) and the MIZ-1-binding elements, MRE-A (bp,-90 to-64) and MRE-B (bp, 27 to 17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp,-95 to-100) and #3 (bp,-55 to-63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.

UR - http://www.scopus.com/inward/record.url?scp=84858335072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858335072&partnerID=8YFLogxK

U2 - 10.1038/onc.2011.331

DO - 10.1038/onc.2011.331

M3 - Article

C2 - 21804610

AN - SCOPUS:84858335072

VL - 31

SP - 1442

EP - 1458

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 11

ER -