Vikram Panse

Biology of molecular machines

The research focus of our laboratory is to unravel the mechanisms by which two large RNA:protein complexes namely, ribosomal subunits (60S and 40S) and mRNPs (mRNA protein complexes) are constructed and targeted to their appropriate functional and cellular location. Further, we are also interested in the regulatory role(s) of SUMO in the dynamic assembly of these large macromolecular complexes. We exploit the powerful combination of genetic, cell biological and biochemical tools available in budding yeast to investigate these processes.

Ribosome Biogenesis and Quality Control

To produce a ribosome, eukaryotic cells must assemble more than 70 ribosomal proteins (r-proteins) with four different rRNA species. In budding yeast the small 40S subunit contains 33 r-proteins and the 18S rRNA, whereas the large 60S ribosomal subunit is composed of 46 r-proteins and three different rRNAs (25S, 5S, 5.8S). In contrast to prokaryotes, eukaryotic ribosome assembly is aided by trans-acting factors which transiently interact with 40S and 60S precursors/intermediates. Proteomic approaches in budding yeast have expanded the inventory of trans-factors (>200 proteins) that are involved in ribosome biogenesis/export. Despite the plethora of factors that have been identified, our knowledge about their spatial and temporal role(s) in promoting ribosomal subunit maturation is rudimentary. Pre-60S and pre-40S subunits are translocated as independent entities through the nuclear pore complex into the cytoplasm where they undergo final maturation steps before achieving translation competence. We are particularly interested in unraveling and dissecting cytoplasmic maturation events that ensure only functional subunits enter translation.

SUMO Biology

Ubiquitin and ubiquitin-like proteins modulate protein function in the cell via reversible post-translational modification. The SUMO proteome strikingly encompasses several nuclear proteins that are part of diverse large multi-subunit machineries. Like ubiquitination, sumoylation is carried out via a distinct enzymatic cascade leading to the covalent linkage of SUMO to the substrate’s lysine residues. De-sumoylation is mediated via desumoylating proteases, making sumoylation a highly dynamic reversible modification. Sumoylation has been shown to affect protein stability, subcellular localization and protein-protein interactions, and is implicated in many cellular processes, such as stress-response, maintenance of chromosomal integrity and stability, regulation of transcription and cellular trafficking. In addition to the covalent attachment of SUMO to target proteins, SUMO has been shown to be able to interact with other proteins also non-covalently. In this case SUMO (either free or substrate-attached) is recognized by a SUMO-interaction motif (SIM), which consists of a short hydrophobic core, usually flanked by a stretch of either negatively charged or phosphorylated residues. Although there has been remarkable progress in unraveling the SUMO proteome, only a handful of SIM-containing proteins have been identified and their functionality characterized. We aim to identify SIM-containing proteins and therefore unravel cellular processes that are regulated by SUMO-SIM interactions.

Review Articles

Maturation of eukaryotic ribosomes: Acquisition of functionality.
Panse VG, Johnson AW.
Trends in Biochemical Sciences. 2010 35(5): 260-66

Sem1- a versatile "molecular glue"?

Faza M, Kemmler S, Panse VG.
Nucleus. 2010 1:12-17

Gle1 does double duty.
Kutay U, Panse VG.
Cell. 2008 Aug 22;134(4):564-6.



Adjunct duties for karyopherins:regulating septin sumoylation.
Panse VG, Hurt E.

Dev Cell. 2007 May;12(5):669-70.



Articles

Yvh1 is required for a late maturation step in the 60S biogenesis pathway.

Kemmler S, Laura Occhipinti, Maria Veisu, Panse VG.

J Cell Biol. 2009 Sept 21;186:863-80.

Sem1 is a functional component of the nuclear pore complex associated mRNA export machinery.

Faza M, Kemmler S, Jimeno S, González-Aguilera C, Aguilera A, Hurt E, Panse VG.

J Cell Biol. 2009 Mar 23;184:833-46.



Formation and nuclear export of preribosomes are functionally linked to the small-ubiquitin-related modifier pathway.

Panse VG, Kressler D, Pauli A, Petfalski E, Gnädig M, Tollervey D, Hurt E.

Traffic. 2006 Oct;7(10):1311-21.



Functional link between ribosome formation and biogenesis of iron-sulfur proteins.
Yarunin A, Panse VG, Petfalski E, Dez C, Tollervey D, Hurt E.

EMBO J. 2005 Feb 9;24(3):580-8.



A proteome-wide approach identifies sumoylated substrate proteins in yeast.

Panse VG, Hardeland U, Werner T, Kuster B, Hurt E.

J Biol Chem. 2004 Oct 1;279(40):41346-51.



Unconventional tethering of Ulp1 to the transport channel of the nuclear pore complex by karyopherins.

Panse VG, Küster B, Gerstberger T, Hurt E.

Nat Cell Biol. 2003 Jan;5(1):21-7.



Electron spin resonance and fluorescence studies of the bound-state conformation of a model protein substrate to the chaperone SecB.

Panse VG, Beena K, Philipp R, Trommer WE, Vogel PD, Varadarajan R.

J Biol Chem. 2001 Sep 7;276(36):33681-8.



A thermodynamic coupling mechanism for the disaggregation of a model peptide substrate by chaperone SecB.

Panse VG, Vogel P, Trommer WE, Varadarajan R.

J Biol Chem. 2000 Jun 23;275(25):18698-703.



Thermodynamics of substrate binding to the chaperone SecB.

Panse VG, Swaminathan CP, Surolia A, Varadarajan R.

Biochemistry. 2000 Mar 7;39(9):2420-7.



Unfolding thermodynamics of the tetrameric chaperone, SecB.

Panse VG, Swaminathan CP, Aloor JJ, Surolia A, Varadarajan R.
Biochemistry. 2000 Mar 7;39(9):2362-9.



SecB binds only to a late native-like intermediate in the folding pathway of barstar and not to the unfolded state.

Panse VG, Udgaonkar JB, Varadarajan R.

Biochemistry. 1998 Oct 13;37(41):14477-83.

Collaborators

Dr. Jens Pfannstiel
Department of Biosensorics, Universitaet Hohenheim, Germany