Characterization of the PR domain of RIZ1 histone methyltransferase

Céline Derunes; Klára Briknarová; Liqing Geng; Sheng Li; Chris R. Gessner; Krissi Hewitt; Shuang Ding Wu; Shi Huang; Virgil I. Woods; Kathryn R. Ely

doi:10.1016/j.bbrc.2005.05.190

Characterization of the PR domain of RIZ1 histone methyltransferase

Céline Derunes
, Klára Briknarová
, Liqing Geng
, Sheng Li
, Chris R. Gessner
, Krissi Hewitt
, Shuang Ding Wu
, Shi Huang
, Virgil I. Woods
, Kathryn R. Ely

Chemistry and Biochemistry

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

RIZ1 (PRDM2) and PRDI-BF1 (PRDM1) are involved in B cell differentiation and the development of B cell lymphomas. These proteins are expressed in two forms that differ by the presence or absence of a PR domain. The protein product that retains the PR domain is anti-tumorigenic while the product that lacks the PR domain is oncogenic and over-expressed in tumor cells. The conserved PR domain is homologous to the SET domain from a family of histone methyltransferases. RIZ1 is also a histone methyltransferase and methylates lysine 9 in histone H3. This activity has been mapped to the PR domain. In the present study, deuterium exchange mass spectrometry was used to define the structural boundaries of the RIZ1 PR domain and to map sites of missense mutations that occur in human cancers and reduce methyltransferase activity. Flexible segments were selectively deleted to produce protein products that crystallize for structural studies. Segments at the carboxyl terminus of the PR domain that are involved in methylation of H3 were shown to be flexible, similar to SET domains, suggesting that the PR and SET methyltransferases may belong to an emerging class of proteins that contain mobile functional regions.

Original language	English
Pages (from-to)	925-934
Number of pages	10
Journal	Biochemical and Biophysical Research Communications
Volume	333
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2005.05.190
State	Published - Aug 5 2005

Funding

This work was supported by Grants CA105347 and CA099835 from the National Cancer Institute, DAMD17-99-1-9093 and DAMD17-02-1-0312 from the USAMRDC, and 4JB-0001 from the California Breast Cancer Research Program. The DXMS work (V.L.W.) also received grant support as technology transfer grants S97-90, S99-44 from the University of California BioStar program and L98-30 from the University of California Life Sciences program with matching partner ExSAR Corporation, Monmouth Junction, NJ. U.S. Patent #5,658,739, U.S. Patent #6,291,189, U.S. Patent #6,331,400, and U.S. Patent #6,599,707 are held by V.L.W. V.L.W. has an equity interest in ExSAR Corporation. The authors are grateful to Lisa O’Brien for preparing the manuscript for publication.

Funder number
DAMD17-02-1-0312, R21CA099835, DAMD17-99-1-9093
4JB-0001, S99-44, S97-90

Keywords

Deuterium exchange
Histone methyltransferases
Mass spectrometry
PR domains
SET domains

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2005.05.190

Cite this

@article{bd9e8fbf511746c6963f45e3534937d6,

title = "Characterization of the PR domain of RIZ1 histone methyltransferase",

abstract = "RIZ1 (PRDM2) and PRDI-BF1 (PRDM1) are involved in B cell differentiation and the development of B cell lymphomas. These proteins are expressed in two forms that differ by the presence or absence of a PR domain. The protein product that retains the PR domain is anti-tumorigenic while the product that lacks the PR domain is oncogenic and over-expressed in tumor cells. The conserved PR domain is homologous to the SET domain from a family of histone methyltransferases. RIZ1 is also a histone methyltransferase and methylates lysine 9 in histone H3. This activity has been mapped to the PR domain. In the present study, deuterium exchange mass spectrometry was used to define the structural boundaries of the RIZ1 PR domain and to map sites of missense mutations that occur in human cancers and reduce methyltransferase activity. Flexible segments were selectively deleted to produce protein products that crystallize for structural studies. Segments at the carboxyl terminus of the PR domain that are involved in methylation of H3 were shown to be flexible, similar to SET domains, suggesting that the PR and SET methyltransferases may belong to an emerging class of proteins that contain mobile functional regions.",

keywords = "Deuterium exchange, Histone methyltransferases, Mass spectrometry, PR domains, SET domains",

author = "C{\'e}line Derunes and Kl{\'a}ra Briknarov{\'a} and Liqing Geng and Sheng Li and Gessner, \{Chris R.\} and Krissi Hewitt and Wu, \{Shuang Ding\} and Shi Huang and Woods, \{Virgil I.\} and Ely, \{Kathryn R.\}",

note = "Funding Information: This work was supported by Grants CA105347 and CA099835 from the National Cancer Institute, DAMD17-99-1-9093 and DAMD17-02-1-0312 from the USAMRDC, and 4JB-0001 from the California Breast Cancer Research Program. The DXMS work (V.L.W.) also received grant support as technology transfer grants S97-90, S99-44 from the University of California BioStar program and L98-30 from the University of California Life Sciences program with matching partner ExSAR Corporation, Monmouth Junction, NJ. U.S. Patent \#5,658,739, U.S. Patent \#6,291,189, U.S. Patent \#6,331,400, and U.S. Patent \#6,599,707 are held by V.L.W. V.L.W. has an equity interest in ExSAR Corporation. The authors are grateful to Lisa O{\textquoteright}Brien for preparing the manuscript for publication. ",

year = "2005",

month = aug,

day = "5",

doi = "10.1016/j.bbrc.2005.05.190",

language = "English",

volume = "333",

pages = "925--934",

journal = "Biochemical and Biophysical Research Communications",

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T1 - Characterization of the PR domain of RIZ1 histone methyltransferase

AU - Derunes, Céline

AU - Briknarová, Klára

AU - Geng, Liqing

AU - Li, Sheng

AU - Gessner, Chris R.

AU - Hewitt, Krissi

AU - Wu, Shuang Ding

AU - Huang, Shi

AU - Woods, Virgil I.

AU - Ely, Kathryn R.

N1 - Funding Information: This work was supported by Grants CA105347 and CA099835 from the National Cancer Institute, DAMD17-99-1-9093 and DAMD17-02-1-0312 from the USAMRDC, and 4JB-0001 from the California Breast Cancer Research Program. The DXMS work (V.L.W.) also received grant support as technology transfer grants S97-90, S99-44 from the University of California BioStar program and L98-30 from the University of California Life Sciences program with matching partner ExSAR Corporation, Monmouth Junction, NJ. U.S. Patent #5,658,739, U.S. Patent #6,291,189, U.S. Patent #6,331,400, and U.S. Patent #6,599,707 are held by V.L.W. V.L.W. has an equity interest in ExSAR Corporation. The authors are grateful to Lisa O’Brien for preparing the manuscript for publication.

PY - 2005/8/5

Y1 - 2005/8/5

N2 - RIZ1 (PRDM2) and PRDI-BF1 (PRDM1) are involved in B cell differentiation and the development of B cell lymphomas. These proteins are expressed in two forms that differ by the presence or absence of a PR domain. The protein product that retains the PR domain is anti-tumorigenic while the product that lacks the PR domain is oncogenic and over-expressed in tumor cells. The conserved PR domain is homologous to the SET domain from a family of histone methyltransferases. RIZ1 is also a histone methyltransferase and methylates lysine 9 in histone H3. This activity has been mapped to the PR domain. In the present study, deuterium exchange mass spectrometry was used to define the structural boundaries of the RIZ1 PR domain and to map sites of missense mutations that occur in human cancers and reduce methyltransferase activity. Flexible segments were selectively deleted to produce protein products that crystallize for structural studies. Segments at the carboxyl terminus of the PR domain that are involved in methylation of H3 were shown to be flexible, similar to SET domains, suggesting that the PR and SET methyltransferases may belong to an emerging class of proteins that contain mobile functional regions.

AB - RIZ1 (PRDM2) and PRDI-BF1 (PRDM1) are involved in B cell differentiation and the development of B cell lymphomas. These proteins are expressed in two forms that differ by the presence or absence of a PR domain. The protein product that retains the PR domain is anti-tumorigenic while the product that lacks the PR domain is oncogenic and over-expressed in tumor cells. The conserved PR domain is homologous to the SET domain from a family of histone methyltransferases. RIZ1 is also a histone methyltransferase and methylates lysine 9 in histone H3. This activity has been mapped to the PR domain. In the present study, deuterium exchange mass spectrometry was used to define the structural boundaries of the RIZ1 PR domain and to map sites of missense mutations that occur in human cancers and reduce methyltransferase activity. Flexible segments were selectively deleted to produce protein products that crystallize for structural studies. Segments at the carboxyl terminus of the PR domain that are involved in methylation of H3 were shown to be flexible, similar to SET domains, suggesting that the PR and SET methyltransferases may belong to an emerging class of proteins that contain mobile functional regions.

KW - Deuterium exchange

KW - Histone methyltransferases

KW - Mass spectrometry

KW - PR domains

KW - SET domains

UR - https://www.scopus.com/pages/publications/20744456917

U2 - 10.1016/j.bbrc.2005.05.190

DO - 10.1016/j.bbrc.2005.05.190

M3 - Article

C2 - 15964548

AN - SCOPUS:20744456917

SN - 0006-291X

VL - 333

SP - 925

EP - 934

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Characterization of the PR domain of RIZ1 histone methyltransferase

Abstract

Funding

Keywords

UN SDGs

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