c-Abl is a proto-oncoprotein expressed in various blood cell lineages. The gene
ID: 260964 • Letter: C
Question
c-Abl is a proto-oncoprotein expressed in various blood cell lineages. The gene encoding Abl was first identified as the oncogene present in the Ableson Murine Leukemia Virus (Ab-MuLV), but was subsequently demonstrated to be a host cell proto-oncogene (c-Abl) that was captured when the provirus integrated into the host cell genome. The v-Abl gene results from a fusion between the viral Gag gene and the cellular c-Abl gene, and thus is also sometimes referred to as Gag-Abl. In normal cells, c-Abl acts in a pathway that induces the expression of immediate-early cell cycle genes when growth factors are present. However, like the BCR-Abl protein that causes Chronic Myelogenous Leukemia in humans, expression of v-Abl/Gag-Abl can cause leukemia in mice.
(A) (5 points) What can you conclude about the structure of the v-Abl/Gag-Abl protein, and why it is an oncoprotein?
(B) (10 points) Other than the specific examples of v-Abl/Gag-Abl and BCR-Abl, suggest two other mechanisms that might convert c-Abl from a proto-oncogene into an oncogene. Your answers can be hypothetical.
(C) (5 points) Why do v-Abl/Gag-Abl and BCR-Abl lead to leukemia? Specifically, which immediate-early gene might be induced by these oncoproteins?
(D) (5 points) With respect to the cell cycle, what is the consequence of expression of the gene from your answer to (C)? Your answer should mention both a specific process, the proteins that regulate this process, and how those proteins are affected by induction of the gene from your answer to (C).
Explanation / Answer
A) v-abl is type of tyrosine kinase receptor, It is overexpressed in many type of cancer such as leukemia, colorectal cancer, hepatocellular carcinoma etc. V-Abl activation occurs in leukemia due to chromosome translocation result in generation of BCR-ABL fusion protein with tyrosine kinase activity.
(B) By following mechanism proto-oncogene converts into onco gene
Point mutations, removal, or addition that leads to a hyperactive gene product
Point mutations, deletions, or insertions in the promoter region of a proto-oncogene that lead to increased transcription
Gene amplification events leading to extra chromosomal copies of a proto-oncogene
Chromosomal translocation events that relocate a proto-oncogene to a new chromosomal site that leads to higher expression
Chromosomal translocations that lead to a fusion between a proto-oncogene and a second gene, which produces a fusion protein with oncogenic activity
(C) following genes induced by oncoproteinsBCR-ABL1, and include the RAS, NF-?B, PI3K-AKT, JUN, ?-catenin, and STAT3 signaling pathway.
(D)The v-Abl1 oncoprotein induces murine lymphosarcoma and acute pre-B cell leukemia.
Related Questions
Navigate
Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.