A majority of the cancer/testis antigens are intrinsically disordered proteins

Krithika Rajagopalan, Steven M. Mooney, Nehal Parekh, Robert H. Getzenberg, Prakash Kulkarni

Research output: Contribution to journalArticlepeer-review

Abstract

The cancer/testis antigens (CTAs) are a group of heterogeneous proteins that are typically expressed in the testis but aberrantly expressed in several types of cancer. Although overexpression of CTAs is frequently associated with advanced disease and poorer prognosis, the significance of this correlation is unclear since the functions of the CTAs in the disease process remain poorly understood. Here, employing a bioinformatics approach, we show that a majority of CTAs are intrinsically disordered proteins (IDPs). IDPs are proteins that, under physiological conditions in vitro, lack rigid 3D structures either along their entire length or in localized regions. Despite the lack of structure, most IDPs can transition from disorder to order upon binding to biological targets and often promote highly promiscuous interactions. IDPs play important roles in transcriptional regulation and signaling via regulatory protein networks and are often associated with dosage sensitivity. Consistent with these observations, we find that several CTAs can bind DNA, and their forced expression appears to increase cell growth implying a potential dosage-sensitive function. Furthermore, the CTAs appear to occupy "hub" positions in protein regulatory networks that typically adopt a "scale-free" power law distribution. Taken together, our data provide a novel perspective on the CTAs implicating them in processing and transducing information in altered physiological states in a dosage-sensitive manner. Identifying the CTAs that occupy hub positions in protein regulatory networks would allow a better understanding of their functions as well as the development of novel therapeutics to treat cancer.

Original languageEnglish (US)
Pages (from-to)3256-3267
Number of pages12
JournalJournal of cellular biochemistry
Volume112
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • CANCER
  • CANCER/TESTIS ANTIGENS
  • DOSAGE SENSITIVITY
  • INTRINSICALLY DISORDERED PROTEINS

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A majority of the cancer/testis antigens are intrinsically disordered proteins'. Together they form a unique fingerprint.

Cite this