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ASCB Newsletter - September 2002

Raikhel, WatermanStorer Selected for WICB Awards

Natasha Raikhel of the University of California, Riverside, and Clare Waterman-Storer of the Scripps Research Institute were selected by the Society’s Women in Cell Biology Committee to receive the 2002 WICB awards.

Raikhel will receive the Senior Award for outstanding work on membrane and protein trafficking through the secretory system to the vacuole in plants, as well as her training and mentorship of young scientists.

Waterman-Storer will receive the Junior Award for her notable use of quantitative light microscopy to study the kinetic parameters of microtubule and actin filament dynamics in living cells.


Ubiquitin Researchers Meet in Colorado

The ASCB began a new series of summer meetings with a highly successful conference on Non-traditional functions of ubiquitin and ubiquitin-like proteins’. The meeting was organized by Cecile Pickart (Johns Hopkins School of Public Health) and Linda Hicke (Northwestern University) and held at Colorado College in Colorado Springs.

As diverse roles for ubiquitin and the growing family of ubiquitin-like modifiers (Ubls) have emerged during the past few years, cell biologists studying processes from the plasma membrane to the nucleus unexpectedly found themselves in the ubiquitin field. This timely meeting brought this newer cadre of ubiquitin enthusiasts together with scientists who have a long-standing focus on the enzymology and function of ubiquitin. In gathering these groups together, the meeting was thus particularly remarkable for the participation of scientists across a broad swath of the ASCB membership.

Ubiquitin is a 76 amino acid protein that becomes covalently linked to other proteins through an isopeptide bond between its Cterminus and a lysine residue within the target protein. In its ‘traditional’ role, ubiquitin monomers are added by linkage of their Ctermini to the lysine 48 (K48) residue of the most recently added ubiquitin, forming polyubiquitin chains. After K48-linked chains reach a length of at least four ubiquitins, they direct proteasomal degradation of the target protein. However, many ubiquitination substrates are modified by single ubiquitin (monoubiquitination) or by chains linked through other lysine residues of ubiquitin (K29or K63-linked chains). These types of ubiquitination confer alternative fates to substrate proteins. Moreover, Ubls (SUMO-1, ISG15, Nedd8, Hub1, etc.) can be conjugated to substrate proteins in a manner similar to ubiquitin, but are not believed to generally confer proteasomal degradation.

One prominent theme of the meeting was the role of ubiquitin in protein trafficking. Monoubiquitination serves as a signal at the plasma membrane, promoting the formation of endocytic vesicles that bud into the cytosol. At the endosomal membrane, ubiquitination promotes the formation of a topologically different kind of vesicle that buds away from the cytosol into the endosomal lumen. Internal vesicles accumulate as the endosome matures and takes on the characteristic appearance of a multivesiclular body (MVB). The limiting membrane of the MVB eventually fuses with the lysosome, resulting in degradation of the vesicles and their contents. David Katzmann, (UCSD) discussed characterization of three protein complexes of vacuolar protein sorting (vps) proteins, which have been designated ESCRT-I, -II and -III (endosomal sorting complex required for transport). These complexes act sequentially to recognize ubiquitinated MVB cargo and target it to intraluminal vesicles. Wes Sundquist (University of Utah) discussed mechanisms whereby the HIV-1 virus appropriates the vps machinery through the cellular protein TSG101, the human ortholog of the ESCRT-I component vps23p, to promote a “reverse budding” of viral particles from the plasma membrane to the exterior of the cell that is topologically analogous to the vps pathway.

Ubiquitin also plays a prominent role in sorting at the trans Golgi network (TGN). Chris Kaiser (MIT) showed that the yeast nitrogen-regulated general amino acid permease (Gap1p) is sorted to the vacuole or plasma membrane through the action of the Bul1p and Bul2p proteins, redundant components of a ubiquitin ligase complex required for Gap1 polyubiquitination. Genetic analysis shows that this decision occurs early in the sorting pathway by directing Gap1p to the endosome, where it can then enter the MVB pathway. Nitrogen regulation modulates the balance between the entry of Gap1p into the MVB and its recycling from the endosome to the Golgi, from whence it can be transported to the cell surface. GGA proteins are involved in the transport of selected proteins from the TGN to the endosome. Interestingly, Annette Boman (University of Minnesota School of Medicine) showed that yeast Gga2p and human GGA2 proteins bind to ubiquitin, suggesting that they may be important components of the machinery that sorts ubiquitinated cargo at the TGN.

Another important theme was the participation of ubiquitin and Ubls in complex regulatory networks, either acting alternately on a single target or at multiple points in a particular pathway. For example, Carsten Hoege (MPI) showed that Smt3, the budding yeast SUMO1 homologue, is conjugated to the replication protein PCNA during S phase. DNA damage induces ubiquitination of the same residues of PCNA, and these two modifications act antagonistically in DNA repair. Rick Firtel (UCSD) provided another elegant example of antagonism by ubiquitin and SUMO-1. The MEK1 kinase is rapidly and transiently SUMOylated in response to chemoattractant stimulation in Dictyostelium, promoting MEK1 activation and translocation from the nucleus to the cortex. Conversely, MEK1 is also ubiquitinated, probably by the nuclear MIP1 ubiquitin ligase, promoting nuclear retention and downregulation of MEK1 after stimulation. Finally, ubiquitin itself acts in multiple ways within the Jak-STAT pathway. James Chen (UT Southwestern) showed that a complex containing the ubiquitin conjugating enzyme Ubc13 and the Ubc-like protein Uev1A acts with the TRAF6 ring domain protein to catalyze K63-linked polyubiquitin chains on TRAF6, leading the activation of the TAK1 kinase. This step does not involve proteolysis, but TAK1 activates a cascade that phosphorylates of Ikb, the inhibitor of the NF-kb transcription factor. As a result, Ikb becomes modified with a K48-linked polyubiquitinated chains and degraded by the proteasome.

In gene regulation, ubiquitin’s role as a transcription activator is closely coupled to its traditional proteolytic function. William Tansey (Cold Spring Harbor Laboratory) showed that the activation domains of many transcription factors are implicated in their ubiquitin-mediated proteolysis. In particular, the short-lived Myc transcription factor is ubiquitinated by the SCFskp2 ubiquitin ligase. Notably, Skp2 and Myc are both oncogenes that alter cell cycle progression and cooperate with Ras in cellular transformation. Remarkably, Skp2 stimulates transcription of Myc target genes in vivo, suggesting that polyubiquitination of Myc is directly related to its activation, and supporting a model in which ubiquitation ‘licenses’ Myc as a transcription factor. Interestingly, oncogenic Myc mutants retain the capacity to be polyubiqutinated, but are degraded more slowly than wild type Myc, suggesting that their oncogenic activity may result from their capacity to remain licensed for an inappropriate length of time. Carilee Denison (UT Southwestern) showed that the 19S regulatory subcomplex of the proteasome is recruited to activated polymerase II promoters, suggesting that overlap in components required for gene activation by ubiquitination and transcription factors degradation may be very extensive indeed.

Finally, there was a great deal of excitement about how ubiquitin is recognized in its various guises. Linda Hicke discussed the recognition of monoubiquitin signals by proteins carrying ubiquitin-interacting motifs (UIMs), ubiquitin-associated domains (UBAs), and a newly-identified ubiquitin interaction motif, the CUE domain. Annette Boman has found that the GGA proteins interact with ubiquitin through motifs that are distinct from previously recognized ubiquitin-binding domains. Moreover, Kay Hofmann (MEMOREC) discussed bioinformational analysis that predicts for yet more domains that may also contribute to ubiquitin recognition. These findings suggest that ubiquitin-binding domains act in a modular fashion to link ubiquitin to related processes.

Together, the presentations and posters of the meeting provided a strong sense that a wealth of complexity may be forecast for the future. We can expect much more exciting and wide-ranging cell biology as we learn how the different ubiquitination chain lengths, linkage types, and ubiquitin-like modifiers within this ‘ubiquitin code’ are utilized, recognized and interpreted.

—Mary Dasso


Gilula, Bernfield Awards Announced

The ASCB has named graduate student Li Wang of Dartmouth College to receive the second annual ASCB-Norton B. Gilula Memorial Award. The Award recognizes an outstanding graduate or undergraduate student who has excelled in research.

Post-doc Christina Hull of Duke University has been selected to receive the ASCB-Merton Bernfield Memorial Award (formerly the ASCB Member Memorial Award). The Award honors a postdoctoral fellow or graduate student who has excelled in research.

Wang and Hull were chosen from a large field of nominees, and will receive honoraria and travel to this year’s ASCB Annual Meeting in San Francisco.


ASCB MAC Honors 13 at the MBL

The ASCB honored thirteen 2002 ASCB/MBL course award recipients at a lunch hosted by ASCB Minorities Affairs Committee Chair Donella Wilson.

The awardees, who received competitive awards from the ASCB through grant funds provided by the NIH/NIGMS/ MARC, and their courses were:

  • Ann Brown of Medgar Evers College for Embryology
  • Susan Campbell of University of Alabama for Neurobiology
  • Kevin Davis of University of Pittsburgh for Physiology
  • Bedrick Gadea of Harvard Medical School for Physiology
  • Joanna Gonsalves of University of California, San Francisco for Frontiers in Reproduction
  • Heather Green of New York University School of Medicine for Biology of Parasitism
  • Faith Harrison of University of Iowa for Microbial Diversity
  • Torrens Javier of New Jersey Medical School, UMDNJ for Frontiers in Reproduction
  • Carolina Livi of California Institute of Technology for Embryology
  • Jason Miranda of University of Texas at Austin for Neural Systems & Behavior
  • Gabriel Pineda of University of Texas Southwestern Medical Center for Physiology
  • Melanie Van Stry of Boston University School of Medicine for Embryology
  • Rebecca Vega of Hopkins Marine Station, Stanford University for Physiology

Also representing the ASCB were former ASCB Secretary and E.E. Just Award recipient George Langford, MAC member Bill Eckberg, Education Committee member Roger Sloboda, Public Policy Committee member Robert Palazzo and E.E. Just Award recipient David Burgess.

ASCB members encouraged award recipients to continue their research careers and to return to the MBL as summer investigators.

2002 is the 17th year that the ASCB and the NIHMARC Program have supported students to attend courses at the MBL


ASCB MAC Supports Histochemical Participants

Twelve students and instructors received funding from the ASCB Minorities Affairs Committee to participate in the “Use of Gold and Gold/Fluorescence for Improved Histology” workshop at the Histochemical Society Meeting, held from July 18–21 in Seattle. They are:

  • Maria Corena, postdoctoral fellow at The Whitney Laboratory of the University of Florida
  • Anthony DePass, associate professor at Long Island University
  • Jennifer Lissade, graduate student at Long Island University
  • Pearl Fernandes, assistant professor at the University of South Carolina
  • Oladapo Yeku, undergraduate student at Long Island University
  • Jacqueline Jordan, postdoctoral fellow at Universities Space Research Association
  • Rui Li, postdoctoral fellow at California State University, Pomona/Northridge
  • Sean McPherson, graduate student at Long Island University
  • Marti Morales, graduate student at New Mexico State University
  • Karen Russell, postdoctoral fellow at Morehouse School of Medicine
  • Joseph Whittaker, associate professor at Morehouse School of Medicine
  • Juliet Wynn, postdoctoral fellow at University of Pittsburgh School of Medicine


MAC Funds Friday Harbor Researchers

Jamilla Harris of Oakwood College, Shawn Arellano of the Oregon Institute of Marine Biology and Raquel Cisneros of Arizona State University received ASCB MAC funding to participate in summer internships in marine research at the Friday Harbor Laboratories of the University of Washington. MAC member Virginetta Cannon of Morehouse College was a summer 2002 investigator at FHL. 2002 is the third summer that the ASCB MAC has supported students at FHL, enabled by the MARC program of the NIH NIGMS.


Members In The News

Mary Hendrix of the University of Iowa, an ASCB member since 1978, is President-Elect of the Association of Anatomy, Cell Biology, and Neurobiology Chairpersons.

Karen Holbrook of the University of Georgia, an ASCB member since 1982, will become the 13th President of Ohio State University on October 1.

Steven Teitelbaum of Washington University, an ASCB member since 1982, is President of the Federation of American Societies for Experimental Biology.


BSCB Names Outstanding Young Scientists

The British Society for Cell Biology has named Alexander Dammermann, a graduate student at the Wellcome Trust Centre for Cell Biology at the University of Edinburgh, Scotland, and Florian Maderspacher, a graduate student at the Max Planck Institute for Developmental Biology, Tübingen, Germany, the Young UK Cell Biologists for 2002.

Dammermann’s thesis focuses on the role of the centriolar satellite protein PCM-1 in centrosome function. His winning abstract is titled, “Assembly of centrosomal proteins and microtubule organization depend on the centroilar satellite protein PCM-1.”

Maderspacher’s winning poster is, “Leopard and Obelix affect cell behaviour during formation of the adult pigment pattern in zebrafish.” He is currently writing his thesis and has been working with a class of zebrafish mutants that specifically affect the behavior of pigment cells in the context of the striped pattern.

Both researchers will attend the ASCB Annual Meeting in San Francisco to present their award-winning posters.


Mayrand to Receive Alberts Award

Sandra Mayrand of the Regional Science Resource Center at the University of Massachusetts Medical School will receive the fifth annual Bruce Alberts Award for Outstanding Contributions to Science Education. The Award will be presented at the 42nd ASCB Annual Meeting in San Francisco.

Announcing the Award, Selection and Education Committee Chair Ken Miller said, “the Award Committee was deeply impressed in the way that Ms. Mayrand’s early volunteer K-12 science education activities have grown into a major science education initiative. She brought researchers and educators together around the focus of experimental cell biology.”

Bruce Alberts, Robert DeHaan and Roger Sloboda also served on the Selection Committee.



The ASCB is grateful to the following members who have recently given gifts to support Society activities:

Bruce Alberts
Allison Berrier
Daphne Blumberg
Juan Bonifacino
Frank Child
Donna Dean
Victor DeLeon
Susan DiBartolomeis
Paul DiCorleto
Caroline Enns
William Epstein
Dan Felsenfeld
Daryl Hartter
Walter Hittelman
Howard Holtzer
Shinya Inoué
Jonathan C.R. Jones
Hynda Kleinman
Ralph Kubo
Jani Lewis
Ulrike Lichti
R.B. Maccioni
Molly Mastrangelo
Satoru Matsuda
Elizabeth McNally
Terry Newcomb
Yukio Okano
Robert Phair
Stephen Pilder
Joel Rosenbaum
William Saxton
Michael Shelanski
Jean-Pierre Simon
Clifford Steer
Joan Steitz
Shirley Tilghman
Robert Trelstad
Kenneth Yamada


CBE to Hold Annual Meeting Reception

Editors of the ASCB’s new journal, Cell Biology Education will host a reception for those interested in learning more about CBE at the ASCB Annual Meeting on Sunday, December 15, from 6:00 pm 8:00 pm

Co-Editors-in-Chief Sarah C.R. Elgin and A. Malcolm Campbell, and other members of the editorial board, will be present to answer questions from ASCB members and other potential authors.

The reception is supported in part by Project Kaleidoscope. Light refreshments will be served.


Grants & Opportunities

NSF Planning and Research Grants. Frontiers in Integrative Biological Research (FBIRE) program. Preliminary Proposals due November 1. Planning grant proposals due November 12.

RPRI Grants. The Research Program on Research Integrity has issued a Request for Applications (RFA).

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