Olle Sangfelt's Group

Our hypothesis is that specific ubiquitin ligases (SCFs) occupy critical positions in oncogenic pathways controlling networks of proteins frequently dysregulated in cancer.

The expression and function of proteins change dramatically following the covalent attachment of the small and highly conserved protein ubiquitin (Ub), in a process known as ubiquitylation. Ubiquitylation controls various cellular functions such as cell growth and division, apoptosis, transcription and repair, among others.

A wealth of experimental evidence reveals that aberrant ubiquitylation of cellular regulators directly contributes to the unchecked proliferation, transcription and death typical of cancer cells, and this system has matured as an important cancer drug discovery arena in recent years.

We use interdisciplinary high-throughput functional analysis in combination with translational studies to identify and functionally characterize cancer candidate ubiquitin ligases. The research is particularly focused on oncogenic SCF ligases with key functions in cell cycle control.

One of the main objectives of our basic research is to explore how specific molecular signals converge to modulate SCF activity and substrate specificity. We are also interested to understand how different biological processes control SCF activity to coordinate cellular responses in normal versus cancer cells. Our translational research aims at identifying powerful prognostic and/or treatment predictive markers in cancer, and novel drugs targeting the activity of a specific SCF ligase or the components involved in the conjugation reaction.

Group Members

Andrä BrunnerPhD student
Mohiuddin GaziAssociated, Postdoc
Aljona MaljukovaAssociated
Olle SangfeltSenior researcher
Aldwin Suryo RahmantoPostdoc

Selected Publications

FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma.
Suryo Rahmanto A, Savov V, Brunner A, Bolin S, Weishaupt H, Malyukova A, et al
EMBO J. 2016 10;35(20):2192-2212

CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer.
Cepeda D, Ng H, Sharifi H, Mahmoudi S, Cerrato V, Fredlund E, et al
EMBO Mol Med 2013 Jul;5(7):1067-86

Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway.
Arabi A, Ullah K, Branca R, Johansson J, Bandarra D, Haneklaus M, et al
Nat Commun 2012 ;3():976

The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling.
Malyukova A, Dohda T, von der Lehr N, Akhoondi S, Akhondi S, Corcoran M, et al
Cancer Res. 2007 Jun;67(12):5611-6

Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line.
Strohmaier H, Spruck C, Kaiser P, Won K, Sangfelt O, Reed S
Nature 2001 Sep;413(6853):316-22

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