Andrei Khokhlatchev

Khokhlatchev, Andrei

Primary Appointment

Research Scientist, Cell Biology

Contact Information

Box 800214

Research Interests

Molecular Mechanisms of Tumor Suppression by NORE1A family of Proteins

Research Description

Our laboratory is interested in Ras signal transduction and the molecular mechanisms

of tumor suppression, specifically within the novel family of tumor suppressors

represented by NORE1 and RASSF1. In humans, Ras is the most common dominant oncogene,

frequently activated by mutation. Ras activation often leads to uncontrolled cell

proliferation and tumor development. Therefore, it is likely that there are molecular

mechanisms in cells that sense the suitability of Ras activation, and in the case

of inappropriate activation, blocks cell proliferation or eliminate the cell.

NORE1 was discovered as a protein capable of binding to activated Ras in vitro

and in vivo with high affinity. Data obtained by us and others suggests that

NORE1, specifically its longest splice isoform NORE1A, is a tumor suppressor,

affected in lung, breast, colorectal, kidney and other cancers. Our hypothesis

is that NORE1 is the key regulator in Ras signaling, determining an outcome

of proliferation or cell cycle arrest or apoptosis. Currently, we are focused

on structure-functional studies of NORE1A to determine and characterize regions

of the molecule essential for growth and tumor suppression, studying mechanism

of NORE1A activation by Ras and identifying components of growth-inhibitory

signal transduction pathway that starts at NORE1A.

RASSF1 is located on human chromosome 3p21, among a cluster of putative tumor

suppressor genes. This cluster is frequently deleted in lung tumors, as well

as in many breast, renal, hepatic, prostate, head/neck and other cancers. Forced

expression of the RASSF1A gene in such tumor cell lines substantially suppresses

their growth rate in vitro and in vivo. RASSF1 is closely related to NORE1;

however, RASSF1 cannot bind Ras. To understand the mechanism of RASSF1A tumor

suppression, we are going to investigate how this protein is activated, specifically

at what conditions it is capable to bind Ras.

Selected Publications