GLTSCR2

GLTSCR2 Full Name

glioma tumor suppressor candidate region gene 2

GLTSCR2 Introduction

GLTSCR2, also known as Nucleophosmin 2 (NPM2) or Spindlin 2 (SPIN2), encodes a nucleolar protein that plays a critical role in maintaining genomic stability and regulating the p53 tumor suppressor pathway. The protein is localized primarily in the nucleolus, a subnuclear structure involved in ribosome biogenesis, stress responses, and cell cycle regulation. Under basal conditions, GLTSCR2 is sequestered in the nucleolus, where it interacts with other nucleolar proteins to maintain nucleolar integrity and regulate ribosomal RNA transcription. Upon DNA damage or oncogenic stress, GLTSCR2 is redistributed from the nucleolus to the nucleoplasm, where it binds to and stabilizes the p53 protein by preventing its MDM2-mediated ubiquitination and degradation. This nucleoplasmic mobilization of GLTSCR2 represents a key mechanism by which cells activate p53-dependent cell cycle arrest and apoptosis in response to genotoxic stress.

Figure 1. The intron and exon organization of NPM2 gene. (Source: Frehlick LJ, et al. 2007)

The tumor suppressor functions of GLTSCR2 have been extensively characterized in various cancer models. Loss of GLTSCR2 expression or function has been observed in several malignancies, including glioma, breast cancer, and colorectal cancer, where it correlates with poor prognosis and therapeutic resistance. In glioma, the GLTSCR2 gene is located within a region of chromosome 19q13.3 that is frequently deleted in high-grade tumors, providing a genetic basis for its loss in this malignancy. Beyond its role in p53 stabilization, GLTSCR2 has been implicated in the negative regulation of type I interferon signaling and antiviral responses, adding another layer of complexity to its functions in immunity and cancer. The protein's ability to integrate stress signals and coordinate p53 activation makes it a potential target for cancer therapy, particularly in tumors with wild-type p53 that may benefit from enhanced p53 stabilization.

Alternate Names for GLTSCR2

GLTSCR2; glioma tumor suppressor candidate region gene 2; glioma tumor suppressor candidate region gene 2 protein; PICT 1; p60; protein interacting with carboxyl terminus 1; PICT1; PICT-1;

• 1. Frehlick LJ, et al. New insights into the nucleophosmin/nucleoplasmin family of nuclear chaperones. Bioessays. 2007 Jan;29(1):49-59.
  2. Lee S, et al. Nucleolar protein GLTSCR2 stabilizes p53 in response to ribosomal stresses. Cell Death Differ. 2012 Oct;19(10):1613-22.