共 114 条
The Paf1 complex: Platform or player in RNA polymerase II transcription?
被引:203
作者:

Jaehning, Judith A.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
Univ Colorado, Sch Med, Program Mol Biol, Aurora, CO 80045 USA Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
机构:
[1] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
[2] Univ Colorado, Sch Med, Program Mol Biol, Aurora, CO 80045 USA
来源:
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
|
2010年
/
1799卷
/
5-6期
关键词:
RNA polymerase II;
Paf1;
complex;
Transcription elongation;
Transcription termination;
Histone modification;
RNA 3 ' end formation;
COTRANSCRIPTIONAL HISTONE MODIFICATION;
TUMOR-SUPPRESSOR PROTEIN;
CARBOXY-TERMINAL DOMAIN;
SACCHAROMYCES-CEREVISIAE;
H2B UBIQUITYLATION;
ELONGATION-FACTORS;
GENE-EXPRESSION;
IN-VIVO;
BINDING PROTEIN;
PROCESSING FACTORS;
D O I:
10.1016/j.bbagrm.2010.01.001
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The Paf1 complex (Paf1C), composed of the proteins Paf1, Ctr9, Cdc73, Rtf1, and Leo1, accompanies RNA polymerase II (pol II) from the promoter to the 3' end formation site of mRNA and snoRNA encoding genes; it is also found associated with RNA polymerase I (pol I) on rDNA. The Paf1C is found in simple and complex eukaryotes; in human cells hSki8 is also part of the complex. The Paf1C has been linked to a large and growing list of transcription related processes including: communication with transcriptional activators; recruitment and activation of histone modification factors; facilitation of elongation on chromatin templates; and the recruitment of 3' end-processing factors necessary for accurate termination of transcription. Absence of, or mutations in, Paf1C factors result in alterations in gene expression that can result in misregulation of developmental programs and loss of control of cell division leading to cancer in humans. This review considers recent information that may help to resolve whether the Paf1C is primarily a "platform" on pol II that coordinates the association of many critical transcription factors, or if the complex itself plays a more direct role in one or more steps in transcription. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:379 / 388
页数:10
相关论文
共 114 条
[91]
Gene loops function to maintain transcriptional memory through interaction with the nuclear pore complex
[J].
Tan-Wong, Sue Mei
;
Wijayatilake, Hashanthi D.
;
Proudfoot, Nick J.
.
GENES & DEVELOPMENT,
2009, 23 (22)
:2610-2624

Tan-Wong, Sue Mei
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

Wijayatilake, Hashanthi D.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

Proudfoot, Nick J.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[92]
An in vivo map of the yeast protein interactome
[J].
Tarassov, Kirill
;
Messier, Vincent
;
Landry, Christian R.
;
Radinovic, Stevo
;
Molina, Mercedes M. Serna
;
Shames, Igor
;
Malitskaya, Yelena
;
Vogel, Jackie
;
Bussey, Howard
;
Michnick, Stephen W.
.
SCIENCE,
2008, 320 (5882)
:1465-1470

Tarassov, Kirill
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Messier, Vincent
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Landry, Christian R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada
Univ Montreal, Ctr Robert Cedergren, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Radinovic, Stevo
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Molina, Mercedes M. Serna
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Shames, Igor
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Malitskaya, Yelena
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Vogel, Jackie
论文数: 0 引用数: 0
h-index: 0
机构:
McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Bussey, Howard
论文数: 0 引用数: 0
h-index: 0
机构:
McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada

Michnick, Stephen W.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada
Univ Montreal, Ctr Robert Cedergren, Montreal, PQ H3C 3J7, Canada Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada
[93]
Drosophila Rtf1 functions in histone methylation, gene expression, and Notch signaling
[J].
Tenney, Kristen
;
Gerber, Mark
;
Ilvarsonn, Anne
;
Schneider, Jessica
;
Gause, Maria
;
Dorsettt, Dale
;
Eissenberg, Joel C.
;
Shilatifard, Ali
.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,
2006, 103 (32)
:11970-11974

Tenney, Kristen
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA

Gerber, Mark
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA

Ilvarsonn, Anne
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA

Schneider, Jessica
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA

Gause, Maria
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA

Dorsettt, Dale
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA

Eissenberg, Joel C.
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA

Shilatifard, Ali
论文数: 0 引用数: 0
h-index: 0
机构: St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA
[94]
A novel collection of accessory factors associated with yeast RNA polymerase II
[J].
Wade, PA
;
Werel, W
;
Fentzke, RC
;
Thompson, NE
;
Leykam, JF
;
Burgess, RR
;
Jaehning, JA
;
Burton, ZF
.
PROTEIN EXPRESSION AND PURIFICATION,
1996, 8 (01)
:85-90

Wade, PA
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824

Werel, W
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824

Fentzke, RC
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824

Thompson, NE
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824

Leykam, JF
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824

Burgess, RR
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824

Jaehning, JA
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824

Burton, ZF
论文数: 0 引用数: 0
h-index: 0
机构: MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824
[95]
Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice
[J].
Wang, Pengfei
;
Bowl, Michael R.
;
Bender, Stephanie
;
Peng, Jun
;
Farber, Leslie
;
Chen, Jindong
;
Ali, Asif
;
Zhang, ZhongFa
;
Alberts, Arthur S.
;
Thakker, Rajesh V.
;
Shilatifard, Ali
;
Williams, Bart O.
;
Teh, Bin Tean
.
MOLECULAR AND CELLULAR BIOLOGY,
2008, 28 (09)
:2930-2940

Wang, Pengfei
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Bowl, Michael R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Churchill Hosp, Nuffield Dept Clin Med, Acad Endocrine Unit,OCDEM, Oxford OX3 7LJ, England Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Bender, Stephanie
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Peng, Jun
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Lab Cell Struct & Signal Integrat, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Farber, Leslie
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Chen, Jindong
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Ali, Asif
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Churchill Hosp, Nuffield Dept Clin Med, Acad Endocrine Unit,OCDEM, Oxford OX3 7LJ, England Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Zhang, ZhongFa
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Alberts, Arthur S.
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Lab Cell Struct & Signal Integrat, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Thakker, Rajesh V.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Oxford, Churchill Hosp, Nuffield Dept Clin Med, Acad Endocrine Unit,OCDEM, Oxford OX3 7LJ, England Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Shilatifard, Ali
论文数: 0 引用数: 0
h-index: 0
机构:
Stowers Inst Med Res, Kansas City, MO 64110 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Williams, Bart O.
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Lab Cell Signaling & Carcinogenesis, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA

Teh, Bin Tean
论文数: 0 引用数: 0
h-index: 0
机构:
Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA
[96]
Characterization of human epigenomes
[J].
Wang, Zhibin
;
Schones, Dustin E.
;
Zhao, Keji
.
CURRENT OPINION IN GENETICS & DEVELOPMENT,
2009, 19 (02)
:127-134

Wang, Zhibin
论文数: 0 引用数: 0
h-index: 0
机构:
NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA

Schones, Dustin E.
论文数: 0 引用数: 0
h-index: 0
机构:
NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA

Zhao, Keji
论文数: 0 引用数: 0
h-index: 0
机构:
NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA
[97]
Rtf1 is a multifunctional component of the paf1 complex that regulates gene expression by directing cotranscriptional histone modification
[J].
Warner, Marcie H.
;
Roinick, Kelli L.
;
Arndt, Karen M.
.
MOLECULAR AND CELLULAR BIOLOGY,
2007, 27 (17)
:6103-6115

Warner, Marcie H.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA

Roinick, Kelli L.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA

Arndt, Karen M.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA
[98]
RLR1 (THO2), required for expressing lacZ fusions in yeast, is conserved from yeast to humans and is a suppressor of SIN4
[J].
West, RW
;
Kruger, B
;
Thomas, S
;
Ma, JL
;
Milgrom, E
.
GENE,
2000, 243 (1-2)
:195-205

West, RW
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA

Kruger, B
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA

Thomas, S
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA

Ma, JL
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA

Milgrom, E
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA SUNY Hlth Sci Ctr, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA
[99]
DEAD-box RNA helicase Sub2 is required for expression of lacZ fusions in Saccharomyces cerevisiae and is a dosage-dependent suppressor of RLR1 (THO2)
[J].
West, RW
;
Milgrom, E
.
GENE,
2002, 288 (1-2)
:19-27

West, RW
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA

Milgrom, E
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA
[100]
A Genetic Interaction Map of RNA-Processing Factors Reveals Links between Sem1/Dss1-Containing Complexes and mRNA Export and Splicing
[J].
Wilmes, Gwendolyn M.
;
Bergkessel, Megan
;
Bandyopadhyay, Sourav
;
Shales, Michael
;
Braberg, Hannes
;
Cagney, Gerard
;
Collins, Sean R.
;
Whitworth, Gregg B.
;
Kress, Tracy L.
;
Weissman, Jonathan S.
;
Ideker, Trey
;
Guthrie, Christine
;
Krogan, Nevan J.
.
MOLECULAR CELL,
2008, 32 (05)
:735-746

Wilmes, Gwendolyn M.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Bergkessel, Megan
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Bandyopadhyay, Sourav
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Bioengn, Program Bioinformat, La Jolla, CA 92093 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Shales, Michael
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Braberg, Hannes
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Cagney, Gerard
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA
Univ Coll Dublin, Conway Inst, Dublin 4, Ireland Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Collins, Sean R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Whitworth, Gregg B.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Kress, Tracy L.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Weissman, Jonathan S.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA
Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Ideker, Trey
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Bioengn, Program Bioinformat, La Jolla, CA 92093 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Guthrie, Christine
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA

Krogan, Nevan J.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA