Pathology & Laboratory Medicine

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Proteolytic Oncogenesis

Pengbo Zhou, PhD, Principal Investigator

Selective degradation of specific cellular proteins by the ubiquitin-proteasome pathway (UPP) is essential for a variety of vital cellular functions. We are interested in aspects of the UPP pertaining to physiological and pathological conditions, including the onset and maintenance of tumor growth as well as drug susceptibility.

Active Projects

  • The role of CRL4 ubiquitin ligase in tumorigenesis and chemotherapy resistance.
  • Ubiquitination and degradation of proteins involved in normal and malignant hematopoiesis.
  • CRL4 function in embryonic development, reproduction, and neurological disease

Active Grants

  • Ubiquitin Ligase Inhibitors as Protective Agents Against Cancer
    PI: Pengbo Zhou, PhD
    The Daedalus Fund For Innovation Research Grant
  • Identification of small molecule inhibitors of the CRL4 ubiquitin ligase
    PI: Pengbo Zhou, PhD
    Sanofi-Aventis
  • Regulation of Nucleotide Excision Repair by Proteolysis
    PI: Pengbo Zhou, PhD
    National Institutes of Health (NIH)
  • Tumorigenic Role of the CUL4A Ubiquitin Ligas
    PI: Pengbo Zhou, PhD
    National Institutes of Health (NIH)

Selected Publications

CDK4/6 Inhibitor PD 0332991 Sensitizes Acute Myeloid Leukemia to Cytarabine-Mediated Cytotoxicity

Pengbo Zhou, PhD

CDK4/6 Inhibitor PD 0332991 Sensitizes Acute Myeloid Leukemia to Cytarabine-Mediated Cytotoxicity

Cancer Res. 2015 May 1;75(9):1838-45.

Yang C, Boyson CA, Di Liberto M, Huang X, Hannah J, Dorn DC, Moore MA, Chen-Kiang S, Zhou P.

PMID: 25744718; PMCID: PMC4417369

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Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases.

Pengbo Zhou, PhD

Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases.

Oncogene. 2014 Feb 20;33(8):986-95.

Kong F, Zhang J, Li Y, Hao X, Ren X, Li H, Zhou P.

PMID: 23416973; PMCID: PMC3930622

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Axl receptor tyrosine kinase expression in breast cancer

Pengbo Zhou, PhD

Axl receptor tyrosine kinase expression in breast cancer

J Clin Pathol. 2014 Aug;67(8):690-6.

D'Alfonso TM, Hannah J, Chen Z, Liu Y, Zhou P, Shin SJ.

PMID: 24904064; PMCID: PMC4549806

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Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus.

Pengbo Zhou, PhD

Merlin/NF2 loss-driven tumorigenesis linked to CRL4(DCAF1)-mediated inhibition of the hippo pathway kinases Lats1 and 2 in the nucleus.

Cancer Cell. 2014 Jul 14;26(1):48-60.

Li W, Cooper J, Zhou L, Yang C, Erdjument-Bromage H, Zagzag D, Snuderl M, Ladanyi M, Hanemann CO, Zhou P, Karajannis MA, Giancotti FG.

PMID: 25026211; PMCID: PMC4126592

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The transcription factor TFII-I promotes DNA translesion synthesis and genomic stability.

Pengbo Zhou, PhD

The transcription factor TFII-I promotes DNA translesion synthesis and genomic stability.

PLoS Genet. 2014 Jun 12;10(6):e1004419.

Fattah FJ, Hara K, Fattah KR, Yang C, Wu N, Warrington R, Chen DJ, Zhou P, Boothman DA, Yu H.

PMID: 24922507; PMCID: PMC4055408

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Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases

Pengbo Zhou, PhD

Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases

Oncogene. 2014 Feb 20;33(8):986-95.

Kong F, Zhang J, Li Y, Hao X, Ren X, Li H, Zhou P.

PMID: 23416973; PMCID: PMC3930622

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The CUL4A ubiquitin ligase is a potential therapeutic target in skin cancer and other malignancies

Pengbo Zhou, PhD

The CUL4A ubiquitin ligase is a potential therapeutic target in skin cancer and other malignancies

Cancer. 2013 Sep;32(9):478-82.

Hannah J, Zhou PB. Chin J.

PMID: 23845142; PMCID: PMC3845565

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Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediated degradation of HOXB4.

Improved ex vivo expansion of adult hematopoietic stem cells by overcoming CUL4-mediated degradation of HOXB4.

Blood. 2013 May 16;121(20):4082-9. 

Lee J, Shieh JH, Zhang J, Liu L, Zhang Y, Eom JY, Morrone G, Moore MA, Zhou P.

PMID: 23520338

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Prostate cancer-associated mutations in speckle-type POZ protein (SPOP) regulate steroid receptor coactivator 3 protein turnover

Pengbo Zhou, PhD

Prostate cancer-associated mutations in speckle-type POZ protein (SPOP) regulate steroid receptor coactivator 3 protein turnover

Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):6997-7002.

Geng C, He B, Xu L, Barbieri CE, Eedunuri VK, Chew SA, Zimmermann M, Bond R, Shou J, Li C, Blattner M, Lonard DM, Demichelis F, Coarfa C, Rubin MA, Zhou P, O'Malley BW, Mitsiades N.

PMID: 23559371; PMCID: PMC3637757

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Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis.

Pengbo Zhou, PhD

Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis.

Cell Res. 2012 Aug;22(8):1258-69. 

Liu L, Yin Y, Li Y, Prevedel L, Lacy EH, Ma L, Zhou P.

PMID: 22453236 

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Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis.

Pengbo Zhou, PhD

Essential role of the CUL4B ubiquitin ligase in extra-embryonic tissue development during mouse embryogenesis.

Cell Res. 2012 Aug;22(8):1258-69. 

Liu L, Yin Y, Li Y, Prevedel L, Lacy EH, Ma L, Zhou P.

PMID: 22453236 

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Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease

Pengbo Zhou, PhD

Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease

Front Oncol. 2012 Mar 6;2:21.

Lee J, Zhou P.

PMID: 22649780; PMCID: PMC3355902

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Maximizing target protein ablation by integration of RNAi and protein knockout

Pengbo Zhou, PhD

Maximizing target protein ablation by integration of RNAi and protein knockout

Cell Res. 2011 Jul;21(7):1152-4.

Hannah J, Zhou P.

PMID: 21606956; PMCID: PMC3129447

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Cullins and cancer

Pengbo Zhou, PhD

Cullins and cancer

Genes Cancer. 2010 Jul;1(7):690-9.

Lee J, Zhou P.

PMID: 21127736; PMCID: PMC2994581

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Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus

Pengbo Zhou, PhD

Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus

Cell. 2010 Feb 19;140(4):477-90.

Li W, You L, Cooper J, Schiavon G, Pepe-Caprio A, Zhou L, Ishii R, Giovannini M, Hanemann CO, Long SB, Erdjument-Bromage H, Zhou P, Tempst P, Giancotti FG.

PMID: 20178741; PMCID:PMC2828953

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SETting the clock for histone H4 monomethylation

Pengbo Zhou, PhD

SETting the clock for histone H4 monomethylation

Mol Cell. 2010 Nov 12;40(3):345-6.

Lee J, Zhou P.

PMID: 21070959; PMCID: PMC3003296

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Navigating the nucleotide excision repair threshold

Navigating the nucleotide excision repair threshold

J Cell Physiol. 2010 Sep;224(3):585-9.

Liu L, Lee J, Zhou P.

PMID: 20458729; PMCID: PMC2897951

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CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis.

CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis.

Mol Cell. 2009 May 14;34(4):451-60.

Liu L, Lee S, Zhang J, Peters SB, Hannah J, Zhang Y, Yin Y, Koff A, Ma L, Zhou P.

PMID: 19481525; PMCID: PMC2722740

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Regulation of DNA damage response pathways by the cullin-RING ubiquitin ligases

Pengbo Zhou, PhD

Regulation of DNA damage response pathways by the cullin-RING ubiquitin ligases

DNA Repair (Amst). 2009 Apr 5;8(4):536-43.

Hannah J, Zhou P.

PMID: 19231300; PMCID: PMC2858918

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DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase

Pengbo Zhou, PhD

DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase

Mol Cell. 2007 Jun 22;26(6):775-80.

Lee J, Zhou P.

PMID: 17588513

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A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins.

Pengbo Zhou, PhD

A kinase-independent function of c-Abl in promoting proteolytic destruction of damaged DNA binding proteins.

Mol Cell. 2006 May 19;22(4):489-99.

Chen X, Zhang J, Lee J, Lin PS, Ford JM, Zheng N, Zhou P.

PMID: 16713579

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REGgamma: a shortcut to destruction.

Pengbo Zhou, PhD

REGgamma: a shortcut to destruction.

Cell. 2006 Jan 27;124(2):256-7.

Zhou P.

PMID: 16439199

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Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase.

Pengbo Zhou, PhD

Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase.

Cell. 2006 Jan 13;124(1):105-17.

Li T, Chen X, Garbutt KC, Zhou P, Zheng N.

PMID: 16413485

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Ectopic targeting of substrates to the ubiquitin pathway

Pengbo Zhou, PhD

Ectopic targeting of substrates to the ubiquitin pathway

Methods Enzymol. 2005;399:823-33.

Zhang J, Zhou P.

PMID: 16338397

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Targeted protein degradation

Pengbo Zhou, PhD

Targeted protein degradation

Curr Opin Chem Biol. 2005 Feb;9(1):51-5.

Zhou P.

PMID: 15701453

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Transient in utero knockout (TIUKO) of C-MYC affects late lung and intestinal development in the mouse.

Pengbo Zhou, PhD

Transient in utero knockout (TIUKO) of C-MYC affects late lung and intestinal development in the mouse.

BMC Dev Biol. 2004 Apr 16;4:4.

Cohen JC, Scott DK, Miller J, Zhang J, Zhou P, Larson JE.

PMID: 15090077; PMCID: PMC419337

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A protein knockdown strategy to study the function of beta-catenin in tumorigenesis.

Pengbo Zhou, PhD

A protein knockdown strategy to study the function of beta-catenin in tumorigenesis.

BMC Mol Biol. 2003 Sep 29;4:10.

Cong F, Zhang J, Pao W, Zhou P, Varmus H.

PMID: 14516475; PMCID: PMC222962

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Exploring the functional complexity of cellular proteins by protein knockout.

Pengbo Zhou, PhD

Exploring the functional complexity of cellular proteins by protein knockout.

Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14127-32.

Zhang J, Zheng N, Zhou P.

PMID: 14593203; PMCID: PMC283557

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CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein.

Pengbo Zhou, PhD

CUL-4A stimulates ubiquitylation and degradation of the HOXA9 homeodomain protein.

EMBO J. 2003 Nov 17;22(22):6057-67.

Zhang Y, Morrone G, Zhang J, Chen X, Lu X, Ma L, Moore M, Zhou P.

PMID: 14609952; PMCID: PMC275435

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